Estrous cycle-dependent variation in amphetamine (AMPH)-stimulated behaviors and striatal dopamine (DA) release were determined for freely moving rats undergoing intracerebral microdialysis. There was greater AMPH-stimulated striatal DA release in the striatum of rats in estrus, during the period from 20 min to 100 min post-AMPH, compared with the response of rats in diestrus (P less than 0.05). Animals in estrus also showed less general activity and greater intensity of stereotyped behaviors than did animals in diestrus (P less than 0.05). Independent experiments examining estrous cycle-dependent differences in AMPH-stimulated striatal DA release in vitro also found that AMPH-stimulated striatal DA release was greater on estrus than on diestrus (P less than 0.05). Thus, striatal DA release and behaviors induced by AMPH are modulated by ovarian hormones. The heightened responsiveness to AMPH during estrus suggests that estrogen and/or progesterone potentiate the striatal DA response to AMPH.