The delta-selective opioid receptor agonist, [D-Pen2,L-Pen5]enkephalin (DPLPE) (10 micrograms i.c.v.), fully generalized to cocaine cue in the rat trained to discriminate 10 mg/kg of cocaine from vehicle. The cocaine-like discriminative stimulus effects of DPLPE were almost completely reversed by naltrindole (56 micrograms i.c.v.), a delta-selective opioid receptor antagonist. In contrast, the mu-selective opioid receptor agonist [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAMGO) (0.03-0.3 micrograms i.c.v.) failed to generalize to cocaine cue. These results suggest that the discriminative stimulus effects of cocaine are mediated through the activation of delta-opioid receptors.