Amphetamine and methylphenidate both inhibited the uptake of 3H-norepinephrine (NE) and 3H-dopamine (DA) although the activity of d-amphetamine was lower with respect to uptake of the 2 catecholamines in synaptosomes from thalamus-hypothalamus and striatum. Cocaine was a much stronger inhibitor of 3H-5-hydroxytryptamine (5-HT) uptake in septum-caudate synaptosomes than amphetamine or methylphenidate. The I50 [50% inhibition] values were 70, 118 and 570 .mu.M for cocaine, methylphenidate and d-amphetamine, respectively. A serotonergic system may be involved in the stimulant properties of cocaine. Differences in pharmacological activities between cocaine and the other 2 stimulants were discussed.