Levels of various G protein subunits were assayed by immunoblot and densitometry, using specific antibodies, in anterior pituitaries and striata of female rats exposed to physiological or pharmacological modifications of ovarian hormone levels and, for comparison, in the same tissues of coeval male rats. Treatment of ovariectomized rats with 17 beta-estradiol 10 micrograms/rat/day for 5, 10 or 20 days induced a time-dependent rise in plasma prolactin (PRL) levels. While no change in G protein levels was observed in the striatum, estrogen treatment induced a significant reduction of all pituitary G protein levels except those of alpha i1, which remained unchanged, and of alpha s42, which increased in a time-dependent manner. A highly significant correlation was observed between pituitary alpha s42 values and plasma PRL levels. During the estrous cycle, pituitary values of alpha o, alpha i3 and alpha s47 were generally lower than those of ovariectomized rats, suggesting the existence of tonic inhibitory influence of circulating ovarian hormones. Pituitary levels of alpha o, alpha i1 and alpha s42 also showed a significant modulation during the various phases of the estrous cycle, and those of alpha o, alpha i3, alpha s47 and beta were significantly lower in female than in male rats. No significant effects of estrous cycle hormone variations or sex differences were observed in the values of striatum G proteins. In conclusion, these data clearly indicate that ovarian hormones, and particularly estrogens, have a significant and specific effect on pituitary G protein levels which may modulate the secretion of pituitary hormones such as PRL.