The present study examined the effects of acute, continuous infusion of nicotine in either the ventral tegmental area or the nucleus accumbens on extracellular concentrations of dopamine in the nucleus accumbens by applying in vivo microdialysis in freely moving rats. Nicotine (1000 microM) infusion for 80 min. in the ventral tegmental area produced a long-lasting increase in accumbal dopamine, whereas similar nicotine infusion in the nucleus accumbens increased dopamine levels only within the first 20 min. of administration. This effect was blocked by systemic pretreatment with the nicotinic receptor antagonist mecamylamine (1 mg/kg, subcutaneously). In contrast to the effects of nicotine, N-methyl-D-aspartate infusion in the ventral tegmental area as well as in the nucleus accumbens produced a long-lasting increase in accumbal dopamine levels. The more procounced effect of infusion of nicotine in the ventral tegmental area as compared to the nucleus accumbens on accumbal dopamine release may be due to a lower rate or even lack of tolerance to nicotine's stimulatory action in the ventral tegmental area. These results support the notion that nicotinic receptors in the ventral tegmental area may be of greater importance than those located in the nucleus accumbens for mediating some of the stimulatory effects of nicotine on the reward-related mesoaccumbens dopamine system.