Prolonged estrogen treatment induced an enlargement of the anterior pituitary gland and finally resulted in irreversible pituitary tumours. Using continuous estrogen delivery [subcutaneous (s.c.) cholesterol-estrogen implants], the effects of ethinyl estradiol and the likewise synthetic estrogens STS 153 and STS 456 have been studied with or without concomitant administration of a progestogen without anti-estrogenic activities (STS 557). There was a dose-dependent prolactin cell-stimulating effect of all these estrogens. Ethinyl estradiol (EE2) had the most marked effect followed by STS 456 which coincides with the relative uterotrophic activity found in rats and mice. The elevated serum prolactin levels in rats with an EE2 implant for 6 months could be reduced slightly but not significantly by apomorphine and reserpine at a daily dose of 100 micrograms/animal and 5 micrograms/animal, respectively. Daily administration of 300 micrograms L-dopa led to a slight but insignificant increase of serum prolactin. The high pituitary weight and serum prolactin levels induced by long-term EE2 treatment were partially reversible after implant withdrawal.