Infections with Vibrio vulnificus resulting in septicemia and high mortality have been correlated with pre-existing liver disease and hemochromatosis. As these conditions are associated with impaired iron metabolism and as iron availability in the host has been implicated in the pathogenicity of a number of bacterial infections, the role of iron as a possible factor in the pathogenesis of V. vulnificus was examined. Injection of mice with iron resulted in a lowering of the 50% lethal dose from 106 to 1.1 cells and in a reduction in the time of death postinfection. Elevated serum iron levels were also produced by damaging livers with injections of CC14. The inoculum size required to kill these mice was directly correlated with serum iron levels. Since the portal of infection of this organism may be by ingestion of contaminated seafood, the effects of iron upon orally induced infection were also studied. The effects of adding iron, transferrin, or Desferal (an iron chelate) upon the growth of V. vulnificus in human and rabbit sera were also examined. Iron appeared to be the limiting factor in the ability of this organism to survive or grow in mammalian sera. These results, both in vitro and in vivo, provided strong evidence that iron may play a major role in the pathogenesis of V. vulnificus. Vibrio vulnificus, a halophilic bacterium, is perhaps the most invasive of vibrio species. Unlike other vibrios, it is associated with a high incidence of septicemia correlated with a high degree of mortality (2, 9). An experimental basis for this invasiveness was demonstrated in laboratory animals by Poole and Oliver (14) and by J. B. Dellinger (M.S. thesis, University of North Carolina, Charlotte, 1980) in histological examinations of ligated ileal loop infections. Blake et al. (2) have provided a comprehensive clinical presentation of infections produced by this bacterium. Seventy-five percent of infections resulting in septicemia were associated with underlying diseases that can result in iron overload. These diseases include hemochromatosis, thalassemia, and chronic cirrhosis. The importance of iron for microorganisms has long been recognized, and the availability of host iron has been proposed as a contributing factor in a number of experimental bacterial infections (1, 3, 18-20). Iron within the mammalian host is bound to various proteins and is, therefore, not readily available for bacterial acquisition (17). For example, the bactericidal or bacteriostatic properties of serum have been attributed to the sequestering of iron by transferrin. These properties can be abolished by increasing the saturation of transferrin with iron (3,5). In view of the high correlation of V. vulnificus infections with diseases involving increased iron status, the effects of iron and iron-chelating agents upon the pathogenicity and upon the ability of this organism to survive in serum were examined. MATERIALS AND METHODS Organisms. V. vulnificus (CDC strain C7184) was used for injections into 6to 8-week-old male mice (ICR) or for inoculation...