The effect of clomiphene citrate (CC) and 17 beta-oestradiol (E2) on oestrogen secretion was studied in human preovulatory granulosa cells in culture. CC stimulated E2 secretion at 1 and 10 ng/ml (respectively, +36 +/- 14% and +33 +/- 5%) in basal conditions but had no effect on FSH-stimulated E2 secretion. On the other hand, E2 had no effect at any of the tested concentrations (0.1 ng/ml to 1000 ng/ml) on its own production. Since the plasma level of CC obtained in clinical use ranges from 1 to 10 ng/ml, this finding could explain the higher plasma oestrogen levels obtained with CC as compared to human menopausal gonadotrophin.