Eight female and 8 male rats were trained to discriminate 5.6 mg/kg i.p. cocaine from saline on 2-lever, food-reinforced drug discrimination procedure. Female rats acquired the cocaine discrimination in approximately the same number of sessions that males did (43 +/- 7 vs. 51 +/- 9 sessions, respectively), and the ED50 for cocaine discrimination was nearly equivalent in female and male rats (2.46 +/- 0.41 vs. 2.32 +/- 0.49 mg/kg, respectively). The time course for cocaine discrimination was similar in female and male rats, except the offset of cocaine's effects occurred significantly earlier in females than in males. D-Amphetamine dose-dependently substituted for cocaine in all 7 males and 6 of 7 females tested, with no significant sex difference in the ED50 values for D-amphetamine substitution. None of the three opioid agonists tested, morphine (mu), U69,593 (kappa) or BW373U86 (delta), fully substituted for cocaine in rats of either sex. The dopamine antagonist fluphenazine blocked the discriminative stimulus effects of cocaine to approximately the same extent in both sexes. Further drug discrimination training with a higher dose of cocaine, 10 mg/kg, did not significantly alter the ED50 for cocaine discrimination, and there was still no significant sex difference in ED50 values (3.50 +/- 0.39 vs. 2.36 +/- 0.41 mg/kg in females vs. males, respectively). In these same rats, however, cocaine (1-10 mg/kg) produced significantly greater locomotor activation in females than in males on a test of spontaneous locomotor activity. Thus, these results suggest that there are few sex differences in discriminative stimulus effects of cocaine, even at doses that produce significantly different locomotor responses in female versus male rats.