Bromocriptine treatment of patients with invasive prolactin (PRL)-secreting pituitary adenomas does not invariably result in normalization of the plasma PRL levels. We previously showed that the antiestrogenic drug tamoxifen inhibited hormone release from transplantable PRL-secreting pituitary tumors in rats. In 8 patients with invasive PRL-secreting pituitary adenomas with extrasellar extension, the effect of the administration of tamoxifen was investigated on the plasma PRL concentration and on the bromocriptine-mediated inhibition of PRL release. Treatment for 5 days with tamoxifen (20 mg/day) suppressed plasma PRL levels as measured in 5 samples over the day significantly by 20 ± 3% (means ± SEM; p < 0.01). During tamoxifen administration the inhibition of PRL secretion by 2.5 mg bromocriptine was further suppressed by 36 ± 7%, in comparison with the plasma PRL levels after bromocriptine alone (p < 0.01).