Amphetamine and methylphenidate both inhibited the uptake of 3H-norepinephrine (NE) and 3H-dopamine (DA) although the activity (as measured by I50 and Ki values) of d-amphetamine was lower with respect to uptake of the two catecholamines in synaptosomes from thalamus-hypothalamus and and striatum. Cocaine was a much stonger inhibitor of 3H-5-hydroxytryptamine (5-HT) uptake in septum-caudate synaptosomes than amphetamine or methylphenidate. The I50 values were 70, 118 and 570 micron for cocaine, methylphenidate and d-amphetamine, respectively. The results of the present study suggested that a serotonergic system may be involved in the stimulant properties of cocaine. It may also explain certain differences in pharmacological activities between cocaine and the other two stimulants as described in the literature.