The catecholaminergic basis of the stimulant actions of amphetamine and morphine was investigated in adult rats treated neonatally with 6-hydroxydopamine (6-OHDA) to produce depletion of cortical catecholamines and marked elevation of norepinephrine in the pons. On days 3, 5, 7 and 9 after birth, rat pups were injected bilaterally in the lateral ventricles with 100, 200, or 400 micrograms of 6-OHDA, dissolved in artificial cerebrospinal fluid (CSF). A control group was injected with the CSF vehicle. The capacity of amphetamine (2 mg/kg) and morphine (1.25, 2.5, and 3.5 mg/kg) to produce behavioral stimulant effects was then subsequently tested in adults. The stimulant effect of amphetamine was attenuated in animals pretreated with 100 and 200 micrograms 6-OHDA and was blocked in those treated with 400 micrograms 6-OHDA. The stimulant effects obtained with morphine were blocked by all 6-OHDA doses (100 and 200 micrograms). For morphine, no tests were made in the 400 micrograms 6-OHDA group on the basis of results obtained in animals pretreated with the lower doses of 6-OHDA. These results are discussed in terms of differing roles played by the catecholamine systems in the production of behavioral stimulation.