To assess a possible inhibitory effect of progestins on PRL secretion, serum PRL and estradiol levels were determined in 13 women with hyperprolactinemia due to a pituitary microadenoma before and after 3 months of treatment with a potent progestin, lynestrenol. PRL levels also were assessed during a TRH challenge test before and after treatment. Results were compared to those obtained in 10 normal women studied during the early follicular phase of their menstrual cycle and at the end of 3 months of treatment. The PRL response to TRH was blunted in patients before lynestrenol therapy. After therapy, basal serum PRL levels were significantly decreased, and the response to TRH was almost abolished. No change occurred in the normal women. The estradiol level was 80.5 +/- 7.5 (+/- SEM) pg/ml in patients before treatment and decreased to 29.2 +/- 5.0 pg/ml after therapy. Therefore, lynestrenol, a potent 19-nortestosterone derivative, exhibits in vivo an anti-PRL effect that could be related to its antiestrogenic and/or androgenic activities.