Experiments were conducted to examine sex differences in striatal dopamine function using in vivo microdialysis in freely moving rats. We report here a sex difference in basal extracellular striatal dopamine determined by quantitative microdialysis (the no net flux method) when castrated and ovariectomized rats were compared. There was no sex difference in dopamine uptake into synaptosomes. This indicates that the sex difference in extracellular dopamine is most likely due to sex differences in dopamine release, synthesis, and/or metabolism. Within 30 min after a single injection (s.c.) of either estradiol benzoate (2.0 micrograms/100 g) or 17 beta-estradiol (1.5 micrograms/100 g) the amphetamine-stimulated release of dopamine was enhanced in the striatum of ovariectomized rats, but there was no effect in castrated male rats. The enhanced amphetamine-induced striatal dopamine release in ovariectomized rats was associated with an enhanced frequency of stereotyped head and limb movements and an increased peak in extra 1/4 turns. There were also sex differences in stereotyped behavior and extra 1/4 turns whether or not animals received estrogen treatment. Thus, there are sex differences in striatal extracellular dopamine and in the effect of estrogen on the striatal dopamine neurochemical and behavioral responses to amphetamine.