There are estrous cycle-dependent differences in amphetamine-stimulated behaviors and striatal dopamine (DA) release; intact female rats exhibit a greater behavioral response to amphetamine on estrus than on other days of the cycle. Following ovariectomy amphetamine-induced behavior is attenuated, as is the striatal DA response to amphetamine in vitro. Repeated estrogen treatment in ovariectomized rats reinstates both of these responses to a level comparable to estrous females. In addition, 30 min after a single treatment with a physiological dose of estrogen there is enhanced amphetamine-induced behavior and increased amphetamine-induced striatal DA detected during microdialysis. This experiment was conducted to determine whether the acute effect of estradiol and the effect of repeated exposure to estrogen are functionally related. We report here that prior treatment with estrogen (three daily treatments of 5 microg estradiol benzoate) results in a significant enhancement of the effect of acute estrogen (5 microg estradiol benzoate) or progesterone (500 microg) on amphetamine-induced striatal DA release and stereotyped behaviors. Both the peak response and the duration of the response are greater in estrogen-primed animals treated with estrogen or progesterone 30 min prior to amphetamine, than in all other groups. Either prior treatment with estrogen (last dose 24 h before) or a single acute injection of estrogen result in an enhanced peak response to amphetamine, with no effect on the duration of amphetamine-induced striatal DA release. Treatment with progesterone in animals not primed with estrogen was not different from treatment with oil vehicle. These results demonstrate that there are both acute and long-term effects of estrogen on the striatum that underlie the dynamic changes in stimulated DA release and amphetamine-induced behaviors during the reproductive cycle.