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The effects of iron-dextran and the iron chelator desferrioxamine B mesylate (Desferal) on the course and outcome of experimental yersiniosis were investigated. Yersinia enterocolitica strains representing the three leading serogroups pathogenic for humans, O3, O8 and O9, were studied. In mice, iron-dextran reduced the median lethal dose of intraperitoneally administered Y. enterocolitica O3 and O9 ca. 10-fold, whereas Desferal reduced this value more than 100,000-fold. Experiments in which Y. enterocolitica was given orally to mice and intraconjunctivally to guinea pigs confirmed that Desferal markedly increased the susceptibility of animals to yersiniosis. Although serogroup O8 yersiniae were inherently more virulent for laboratory animals, they were less affected by Desferal than were O3 or O9 strains. In vitro experiments indicated that Desferal promoted growth of Y. enterocolitica under iron-limiting conditions and suggested that the enhanced virulence of O8 yersiniae may be due to their comparatively low requirement for iron. The adverse effect of Desferal on the course of experimental infection with Y. enterocolitica may partly explain the heightened susceptibility of iron-overloaded patients to systemic yersiniosis.