The aim of this study was to explore the direct action of histamine on progesterone and estradiol secretion of human granulosa cells cultured in serum-free medium. Human granulosa cells were isolated from preovulatory follicular fluid aspirated from 17 women (32 +/- 3 years old, mean +/- SD) undergoing in vitro fertilization treatment at the University Women's Hospital of Tübingen. Progesterone and estradiol production was measured in the presence and absence of histamine, terfenadine or cimetidine using radioimmunoassays. Statistical analysis of the data was performed by analysis of variance and Newmann-Keul tests. Histamine stimulated a dose-related increase in estradiol secretion with a maximal stimulatory effect at 10(-3) mol/l. This response was blocked specifically by the H1-receptor antagonist terfenadine. Progesterone production in response to histamine stimulation was independent of dose at the limit of significance. The specific H2-receptor antagonist cimetidine did not block the stimulatory effect of histamine. We suggest that histamine has a direct stimulatory effect on steroid production of granulosa cells mediated via the H1-receptor. This effect may have a physiological role in the regulation of granulosa cell function during the menstrual cycle.