The effects of H1-antagonists, such as tripelennamine, chlorpheniramine and pyrilamine, on the discriminative stimulus effects of cocaine and methamphetamine in rats were examined. Rats were trained to discriminate between cocaine (10 mg/kg, Lp.) or methamphetamine (1.0 mg/kg, Lp.) and saline, with responses maintained under a fixed-ratio 10 (FR10) schedule of food delivery. In generalization tests, tripelennamine generalized to the discriminative stimulus effects of cocaine and methamphetamine, while chlorpheniramine only generalized to cocaine. These generalizations of tripelennamine and chlorpheniramine were attenuated by the dopamine receptor antagonist haloperidol. Furthermore, tripelennamine and chlorpheniramine, but not pyrilamine, potentiated the discriminative stimulus effects of cocaine and methamphetamine. These results suggest that some H1-antagonists possess cocaine- and/or methamphetamine-like discrminative stimulus effects which may be mediated by the dopaminergic system, and as a result the discriminative stimulus effects of cocaine and methamphetamine were potentiated by these H1-antagonists.