This study with monkeys was designed to answer two questions. 1) Does acute nicotine preferentially release more dopamine in the striatum than in the prefrontal cortex? 2) Do repeated doses of nicotine produce sensitization of striatal dopamine release? Microdialysis techniques were used to measure extracellular dopamine in both brain regions in two separate groups of conscious animals. The acute nicotine i.v. dose schedule was a bolus of 32 microg/kg plus an infusion of +/-0.8 microg/kg/min and a 100 microg/kg bolus plus an infusion of +/-2.53 microg/kg/min for 30 min to mimic human tobacco smoking arterial plasma nicotine concentrations. Acute nicotine given i.v. released more dopamine in the striatum than in the prefrontal cortex. In the second experiment, for convenience, daily nicotine was given i.m. and not i.v. bid in doses of 32 or 100 microg/kg for nine days. Dopamine release was measured after overnight nicotine abstinence using the i.v. dose schedule from the first experiment. Baseline dopamine release was significantly reduced (77.6% of control, P<0.05). With a lowered baseline, a greater facilitation of dopamine release was produced by nicotine compared to that obtained under control conditions when the baseline was higher. The impaired dopamine release with overnight nicotine abstinence was transiently enhanced in a dose dependent manner. These data regarding the striatum are consistent with previous findings in rodents of nicotine sensitization of dopamine release especially in nucleus accumbens following repeated administration.