The involvement of dopamine (DA) receptor subtypes in the behavioral effects of CNS stimulants was studied in rats trained to discriminate cocaine from saline. In substitution tests, the stimulus effects of 10 mg/kg of this substance generalized to d-amphetamine (0.25-1.0 mg/kg) and the selective D2 against LY-171555 (0.05-0.25 mg/kg) but not to the D1 agonist SKF-38393 (5.0-15.0 mg/kg); in combination tests, the D1 antagonist Sch-23390 (0.0625-0.5 mg/kg) significantly blocked, and the D2 antagonist spiperone (0.25-0.5 mg/kg) partially blocked the cocaine cue. These data suggest that the involvement of DA systems in the behavioral effects of cocaine is more complex than either D1 or D2 receptor activation; for example, the stimulus properties of this substance might involve both D1 and D2 receptor activation.