A 30-year-old patient with primary infertility had a history of recurrent oral and perineal rashes that appeared just prior to the midcycle rise in basal body temperature and subsided with the onset of menses. The rashes did not appear during periods of treatment with oral contraceptives or danazol, and were suppressed by administration of cortisol. Sera obtained during the follicular and luteal phases of her cycle were found to contain a progestin-binding component with high affinity for 17-hydroxyprogesterone and a somewhat lower affinity for progesterone. Analysis of these sera showed the progestin-binding component to have properties of IgG, with an apparent binding affinity for 17-hydroxyprogesterone of 2 X 10(10) M-1. This report is the first characterization of an antibody to an endogenous steroid in human serum.