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Le Capitaine Flam, l'androïde Mala, le robot Crag et le professeur Simon accompagnés de l'agent spéciale Johann Landore, entament une course contre la montre. Sur la planète Dénef, une terrible épidémie fait des ravages dans la population. Il faut trouver le remède qui stoppera les effroyables mutations. Pour toute piste, quelques mots prononcés par un agent contaminé : "L'Empereur Éternel, rétrogradation de l'espèce". Le Capitaine Flam et ses compagnons parviendront-ils a? revenir sains et saufs de cette mission ? Devant aller au-delà? de ses limites pour faire face au mystérieux Empereur Eternel, Flam, hante? par son passe?, risque d'y perdre son a?me.
Pour rembourser ses dettes, Denji, jeune homme dans la dèche la plus totale, est exploité en tant que Devil Hunter avec son chien-démon-tronçonneuse, “Pochita”. Mais suite à une cruelle trahison, il voit enfin une possibilité de se tirer des bas-fonds où il croupit ! Devenu surpuissant après sa fusion avec Pochita, Denji est recruté par une organisation de Devil Hunters et part à la chasse aux démons...
L'histoire se déroule en Allemagne, en 1986, à Düsseldorf. Kenzo Tenma, le personnage principal, est un jeune neurochirurgien très talentueux, destiné à une brillante carrière et fiancé à la fille du directeur de l'hôpital, Eva Heinman. Mais un jour il refuse de soigner le maire et préfère soigner un garçon blessé d'une balle dans la tête. Sa sœur jumelle est aussi internée dans l'hôpital car elle est très choquée. Leurs parents (adoptifs) ont été assassinés sauvagement. Le garçon s'en sort, mais le maire meurt, faute de soins. Tenma est alors rétrogradé par le directeur de l'hôpital et Eva le quitte. Peu de temps après, le garçon et sa sœur disparaissent. Neuf ans plus tard alors que Tenma est sur le point de devenir le directeur d'hôpital, il est accusé de meurtre qui ont en fait été commis par Johann, ce garçon de 11 ans qu'il avait sauvé. Dès lors l'inspecteur Rünge, un homme de caractère et de confiance prend en charge l'enquête. Il poursuit Tenma sans relâche tandis que ce dernier poursuit Johann ; car Tenma, qui se demande s'il n'a pas sauvé un "Monstre", sait que les meurtres sont "l'œuvre" de son ancien patient.
