We have examined the effects of nonsteroidal antiestrogens (AEs) and estradiol (E) on dopamine (DA) levels and turnover rates in the medial basal hypothalamus (MBH) and on serum and pituitary PRL to gain insight into DA-PRL-E/AE interrelationships. In 21-day-old female rats, E was found to increase MBH DA levels and turnover and serum PRL concentrations in a time- and concentration-dependent manner. Changes were observed by 1 day, and after 3 days of E treatment (1 microgram/day), MBH DA levels increased 2-fold (to 1300 pg/mg tissue), and DA turnover rates increased 5-fold (to 1170 pg/mg tissue . h). The AEs tamoxifen, monohydroxytamoxifen, CI628, and LY117018 (50 micrograms/day for 3 days) weakly stimulated uterine weight gain and significantly suppressed the uterotropic action of E. The AEs LY117018, monohydroxytamoxifen, CI628, and tamoxifen competed with E for binding to the MBH estrogen receptor and displayed relative binding affinities of 190%, 185%, 6.7%, and 1.4%, with E set at 100%; these affinities are similar to those found for uterine estrogen receptors. The AEs increased DA turnover rates only 2-fold, and they antagonized the E-induced 5-fold increase in DA turnover rates very successfully. In animals treated with bromocriptine, E and AE failed to increase the low serum PRL levels, yet they evoked significant (approximately 2-fold) increases in DA turnover rates and nearly 2-fold increases in MBH DA content. Hence, a part of the actions of E and AE on MBH DA appears to be exerted independently of changes in circulating PRL and may occur by direct action of these compounds on the estrogen receptor system present in the MBH. In addition, these studies reveal that AEs behave as partial estrogen agonists/antagonists in terms of their effects on MBH DA turnover.