Candidal vaginitis most often recurs during pregnancy and in the late luteal phase just before menstruation. We examined the influence of the stage of the menstrual cycle on the cellular immune response to Candida albicans, the efficiency of C. albicans germination in sera, and the ability of products from activated lymphoid cells to inhibit germination. C. albicans germination was maximal in sera obtained during the luteal phase. During this period the cellular immune response to Candida was reduced as was the inhibition of Candida germination by products of activated peripheral blood mononuclear cells. Variations in immune response to Candida were of much lesser magnitude in women who took oral contraceptives, which suggests that it was the marked fluctuation in progesterone or estradiol levels during the menstrual cycle that influenced the changes in the immune response to C. albicans. Thus the hormonal status of women may influence the pathogenicity of C. albicans by modulation of immune system activity. These results explain the clinical observation that candidal vaginitis infections most frequently reappear before menstruation.