Studies using an experimental model of the mouse and Candida albicans as the challenge organism attempted to define better the mechanism of nonspecific resistance to infection induced by bacterial endotoxins. In vitro studies showed a positive correlation between the growth of C. albicans in serum from mice obtained at daily intervals for 10 days after endotoxin or saline injection and the percentage iron saturation of the serum. In vivo studies in which one of four different concentrations of iron as ferric ammonium citrate was injected into control and endotoxin-treated mice at the time of challenge with C. albicans showed that the rate of mortality of the mice was directly related to the concentration of iron injected. The endotoxin-induced nonspecific resistance was negated and reversed by iron administration. These studies demonstrate that changes in iron metabolism induced by bacterial endotoxin are a key factor in the mechanism of resistance to C. albicans infection in mice.