The present study examined the action of nicotine on the accumulation of [3H]dopamine into synaptic vesicles prepared from mouse cerebral cortex or bovine striatum. Nicotine was shown to be a weak inhibitor of [3H]dopamine accumulation, with an IC50 of approximately 0.2-0.4 mM. In addition, repeated nicotine administration (1.2 mg (-)-nicotine di-(+)tartrate/kg s.c., twice daily for 10 days) in vivo in BALB/cBy male mice did not alter the potency of reserpine in inhibiting [3H]dopamine accumulation into synaptic vesicles, nor did it change the slight shift induced by nicotine in the potency of reserpine in inhibiting [3H]dopamine accumulation. The present results show that nicotine is an inhibitor of vesicular dopamine accumulation at high concentrations.