Plasma prolactin levels rise in stimulated cycles. To clarify the effects of gonadotrophin on the lactotrophs, three studies were performed. First, plasma concentrations of prolactin during clomiphene citrate (CC)-human menopausal gonadotrophin (HMG)-human chorionic gonadotrophin (HCG) treatment of women enrolled for in-vitro fertilization (IVF) were compared with those during HMG-HCG administration while under pituitary suppression with a gonadotrophin releasing hormone (GnRH) analogue (buserelin). Women suppressed with buserelin had higher basal levels of PRL in plasma (14.4 +/- 4.3 ng/ml versus 6.9 +/- 1.4 ng/ml, P less than 0.001). Only buserelin-suppressed women showed a significant rise in plasma prolactin before HCG administration, while both patient groups had marked prolactin peaks after HCG injection. This peak was higher in the buserelin group (71.9 +/- 50.7 ng/ml versus 52.6 +/- 29.7 ng/ml). The second study showed that plasma levels of prolactin of 6 post-menopausal women were significantly increased 48 h after an injection of 5000 IU HCG, i.m. (24.9 +/- 17.4 ng/ml versus 12.4 +/- 6.2 ng/ml P less than 0.05). Third, plasma prolactin was studied in 5 women over 30 days after surgical castration. An upward trend was observed similar to that of endogenous gonadotrophin, with the change in prolactin values closely correlating with the change in concentrations of follicle stimulating hormone (P less than 0.005). All these findings suggest that human gonadotrophins stimulate lactotrophs.