Plot
Below is a summary for the past twenty-two volumes in chronological order.
Aboard the ship Advenna Avis in 1711, a group of alchemists summon a demon in the hopes of gaining eternal life. The demon gives them an elixir of immortality and the method of ending their existence, by "devouring" one another, and grants the summoner Maiza Avaro the formula of the elixir. Maiza and most of the alchemists decide that no one else must become immortal; only Szilard Quates opposes. That night, the alchemists begin to disappear, devoured by Szilard. Realizing the threat posed by staying together, they scatter across the globe.
In New York City during November 1930, Szilard succeeds in recreating the elixir, only to have it stolen by young thug Dallas Genoard. The elixir continually moves around the city because of Dallas, with the three mafiosi Gandor brothers, the two idiotic thieves Isaac Dian and Miria Harvent, and Maiza's protege Firo Prochainezo and their Camorra family, the Martillo, all passing it around. Szilard makes Dallas an incomplete immortal (meaning he still ages) to retrieve the elixir. However, all other parties accidentally consume the elixir, mistaking it for alcohol, at a party for Firo. Firo falls in love with Szilard's immortal homunculus Ennis, who betrays Szilard by telling Firo how to devour Szilard, which he does. The Gandor then cement Dallas to a barrel at the bottom of the Hudson River to punish him for killing Gandor members.
In late 1931, the Gandor fight the Runorata family for control of the same area after a new drug surfaces. In an attempt to resolve the situation, Luck Gandor asks his adoptive brother Claire Stanfield, an assassin and train conductor, to travel to New York. Claire agrees to, and as a conductor, boards the transcontinental train the Flying Pussyfoot. The train is hijacked by the Russo and Lemure gangs, who are trying to kidnap a senator's family, and a battle ensues between the two gangs. Jacuzzi Splot, Nice Holystone and their gang attempt to protect the passengers and fight the hijackers, while Claire assumes the identity of the Rail Tracer, a monster that eats train passengers, and slaughters much of the Russo and the Lemure. During a confrontation between Ladd Russo and Chane Laforet and the Lemure, Claire interrupts and proposes to Chane Laforet, who is the daughter of Huey Laforet, one of the original immortals aboard the Advenna Avis. A serial stowaway and newspaper field agent named Rachel flees Claire and ends up helping in the rescue of the hostages. The last remaining members of the Lemure are eventually defeated by Jacuzzi's gang, while sadistic murderer Ladd Russo is incarcerated and loses his arm to Claire. At the same time, Ennis writes to Isaac and Miria, inviting them to Manhattan. The duo boards the same train and meets Jacuzzi, and unwittingly sway immortal Czeslaw Meyer from enacting malevolent acts via bombs to be used in the New York Drug War.
The train arrives in New Year 1932 with the survivors going their separate ways: Jacuzzi and Nice escape custody and go into hiding after their base of operations in Chicago was taken over by the Russo family; information gatherer Rachel returns to the Daily Days mostly unscathed; Isaac and Miria introduce Czes to the Martillo family and is subsequently adopted by Firo and Ennis, who later marry, as the latter's brother; and Claire begins his mission to exterminate the enemies of his adoptive brothers, with his intentions to find Chane and marry her after the job is done.
Later that year in 1932, Dallas' sister Eve searches for Dallas, putting her at odds with the Gandor family. These stories involved the Daily Days News Information company and the Runorattas' drug plot with Begg, a drug-addicted immortal alchemist acquaintance of Maiza's encroaching Gandor turf through his miracle drugs, testing it on innocent bystanders including a young man named Roy Maddock. Eventually Eve is caught up in the turf war involving drugs with the Runoratta family and Gandors, the ramifications of the turf war affecting two lovers: Gandor speakeasy waitress Edith and her boyfriend, revealed to be Roy. The climax of the conflict results in Luck secretly telling Eve where Dallas is to spare her from bloodshed, and with Claire's help, the turf war ends with bittersweet results for Edith and Roy now associated with the Gandors until they finish the debt they compiled in the story albeit in happier terms.
Eventually in 1933, Dallas is pulled out of the river, but shortly after, he is abducted by the Larvae, a group working for Huey Laforet. Meanwhile, Jacuzzi's operations begin to encroach on Gandor and Martillo turf. Representatives (Ronnie Schiatto, Ennis, Maria Barcelito and Tick Jefferson) from both groups converge on Eve's home, where his gang is staying along with Isaac and Miria. At the same time, the Larvae arrive to enlist Jacuzzi's help; they have kidnapped Dallas to prove that immortality is possible, and attempt to convince Jacuzzi into join them. However it devolves into an incident at the mansion, forcing both parties to temporarily retreat and attract the attention of Claire after hearing Chane was injured in the battle. Their conflict reaches a prominent building in New York called Mist Wall, the largest branch office of the military equipment researcher and developer Nebula, is bombed according to Huey's plan but mitigated by the intervention of various parties involved. The gangs avert further catastrophe by stopping the Larvae group and with Tick Jefferson making amends with Larvae leader Tim, revealed to be his lost younger brother before once again going their separate ways.
The next year in 1934 at Alcatraz Island, Ladd Russo befriends Firo, who was framed by fellow Immortal Victor Talbot for the Mist Wall public bombing and Isaac, who was finally caught for his thefts, leaving Miria morose from his arrest. All three men meet Huey Laforet in separate occasions, who was charged with treason and conspiracy years ago with affiliation to the Lemures among other terrorist acts. Meanwhile, Christopher Shouldered, Huey's homunculus, and Graham Specter, Ladd's loyal follower, cause an all out war in Chicago through various battles enacted by the Lamia, Nebula and the Russo family led by a now immortal Placido Russo with each battling for their lives. Afterwards, Jacuzzi and his gang return to Chicago while Ladd attempts to kill Huey and fails thanks to the efforts of Isaac, Firo and Chane's homunculus sister, Leeza Laforet; however, the scuffle resulted in Huey's eye taken with the help of Lamia operative Sham, a homunculus who can take over one's consciousness by contact through his body in the form of water. The homunculus group Lamia (associated with Larvae, the group previously encountered by the cast in 1933) cause trouble for the Russo family while this happens. Several of the Lamia join their forces and others split after the conflict, particularly Christopher joining with the Russo family to protect the androgynous heir Ricardo Russo along with Lamia member Sickle and Graham Spector. Isaac is eventually released from Alcatraz along with Firo after fulfilling their mission. Placido Russo, Ricardo's grandfather and Ladd's uncle, is eventually turned immortal and consumed by Nebula scientist Renee for his failure in stopping the rampage of Chicago, resulting in Ricardo inheriting the crime family.
The remainder of the plot focuses on an even older faction of immortals led by Huey's mentor and former lover, Renee Paramedes Branvillier, who details their relationship with the 1711 immortals from the 1700s till the later 1930s and how the corporation Nebula involves themselves against the other crime families by allying themselves with Senator Manfred Beriam, who bears malevolent grudges against immortals.
In 1935, one particular immortal named Melvi targets Firo in by manipulating the entire cast to partake in a high stakes casino royale party in a newly established building called Ra's Lance run by various Mafia families, however many other characters have various agendas that threatens his plan. He intends to endanger Ennis in order to extract the memories of Szilard Quaites by eating Firo, unaware that his bodyguard is Claire Stanfield, resulting in his defeat. Later, Renee continues to pursue Huey by attempting to reclaim their daughter Chane for an experiment which put her at odds with Claire who intends to marry their daughter. As of this writing, the conflict remains unresolved.
In 2001, Maiza and a few immortals appear in a rural European town to apprehend a fellow alchemist and immortal Elmer C. Albatross, who had been masquerading as a demon and was imprisoned by the locals. They uncover an age old conspiracy detailing the origins of water homunculi from the 1930s (Sham and Leeza Laforet, sister of Chane) and also putting a stop the experiments on the people that had been ongoing in the town as they remained unaware of Szilard Quaite's demise for almost the remaining century, his descendant Bild Quaites later encounters the immortals and reveals the horrific secrets of the village. Phil and Felt Nebil, homunculi resulting from Szilard's experiments are subsequently freed from the village and allowed to wander the earth, ending up in New York after the ordeal.
In 2002, a cult named SAMPLE launches a heist to replicate the Flying Pussyfoot incident via a twin cruise ship named Exit and Entrance only to be thwarted by Claire Stanfield and Chane Laforet's descendants, Claudia and Charon Walken with Jacuzzi Splot and Nice Holystone's descendant, Bobby Splot along with his gang with unwitting aide from another faction called Mask Makers led by Huey's descendant Luchino B. Campanella. It is eventually revealed that Czes's tormentor Fermet is in fact the mastermind and overall villain of the series after Szilard Quates.