The multiple effects of estrogens on infectious processes are only beginning to be understood. The existence of such effects is suggested by gender-related differences in the incidence and severity of some infections and by the association of certain infections with predictable hormonal changes. Current information indicates that estrogens may depress cell-mediated immunity, impair the activity of natural killer cells, and suppress some aspects of neutrophil function. Estrogens potentiate the production of systemic antibody, but local antibody responses may be impaired. Direct effects of estrogens on microorganisms have thus far been best studied in fungi; these hormones may either stimulate or suppress fungal virulence, depending on the species involved. Recent research also suggests responsiveness to estrogens in a wider variety of microorganisms. Studies in cell culture, animals, and humans indicate that pregnancy, estrogen supplementation, and menstrual stage can affect the acquisition and severity of certain bacterial, parasitic, and viral infections. This interaction depends on multiple attributes of both the microbe and the host in a given setting and thus may lead to disparate outcomes; however, there appears to be a predisposition to increased infectious morbidity in certain high-estrogen states. In view of the widespread use of estrogen supplementation, the clinical impact of estrogens on the incidence and outcome of infection needs to be better defined.