The nigrostriatal dopamine (DA) system is sexually dimorphic. In female but not male rats, striatal DA activity is modulated by gonadal steroid hormones. Ovariectomy (OVX) decreases striatal DA release and turnover. Estrogen replacement restores the response to that of the intact female in estrus. In contrast, castration (CAST) of male rats has no effect on the stimulated release of DA from striatal tissue. This report addresses the question: Does estrogen act directly on the striatum to induce changes in DA release? Physiological concentrations of 17p-estradiol and other steroids or a nonsteroidal estrogen analog were applied directly to striatal tissue maintained in an in vitro superfusion system. The effect of hormonal treatments on the responsiveness of striatal DA terminals to stimulation was examined in tissue from OVX females and intact and CAST male rats. The results are summarized as follows: (1) Infusion of 17P-estradiol (p < 0.01) and diethylstilbesterol (p < 0.05) increased amphetamine (AMPH)-stimulated striatal DA release from striatal tissue of OVX female rats compared with the effect of cholesterol. 17alpha-Estradiol also tended to potentiate the striatal DA response to AMPH, but this result was not statistically significant (p < 0.062). 17p-Estradiol had no effect on AMPH-stimulated DA release from striatal tissue of intact male rats. (2) The KC1-stimulated release of DA from striatal tissue of OVX rats exposed in vitro to 100 pg/ml 17P-estradiol (a physiological dose) was significantly greater (p < 0.05) than the response after exposure to vehicle. In contrast, 1,000 pg/ml 17P-estradiol produced a decrease in KC1-induced striatal DArelease (p < 0.05), whereas 17alpha-estradiol(lOO pg/ml or 1,000 pg/ml) did not significantly influence the response to KC1. (3) The pulsatile administration of 17P-estradiol stimulated DA release from strital tissue of OVX females (p < 0.05; compared with tissue from an OVX group that received vehicle or CAST male rats exposed to either 17P-estradiol or vehicle). It is concluded that with tissue from OVX rats, physiological concentrations of estrogen can act directly on striatal tissue in vitro to stimulate DA release and to increase striatal DA responsiveness to stimulation, whereas prolonged exposure or high concentrations of 17P-estradiol decreases striatal DA responsiveness. The striatum and/or the striatal DA system are sexually dimorphic in this regard.