Administration of the antiestrogen tamoxifen to normal Buffalo female rats caused a 45% reduction (p < 0.01) in 3H-prolactin synthesis and release in vitro. Radioimmunoassayable prolactin in incubated glands and medium also decreased significantly. Similar results were observed in Wistar-Furth animals except for in vitro radioimmunoassayable prolactin, which decreased less markedly (by 33%, p < 0.01). Serum prolactin concentration in treated rats was unchanged. Tamoxifen did not affect the extremely high serum prolactin concentration in rats bearing mammotropic tumors. It further reduced in vitro synthesis of radioactive prolactin but not of the radioimmunoassayable hormone. No interaction between antiestrogens and the dopamine agonist bromocriptine was observed. These observations suggest that the nonsteroidal antiestrogens decrease the synthesis of prolactin but have little effect on release of the hormone. Tamoxifen inhibits growth of transplantable mammotropic tumors MtTW15 and 7315a potently without altering tumor prolactin production. In vivo treatment of adult female rats with tamoxifen did not affect in vitro synthesis and release of radioactive growth hormone, but reversed the elevated growth hormone production of rats bearing 7315a tumors.