In vivo microdialysis was used to measure the effect of chronic “binge” pattern cocaine administration on basal and cocaine‐induced dopamine levels in the caudate putamen and nucleus accumbens of C57BL/6J and 129/J mice. Mice were implanted with a guide cannula in the caudate putamen or nucleus accumbens and after 4 days recovery, one group received “binge” pattern cocaine administration for 13 days (15 mg/kg × 3, i.p. at hourly intervals) while another group received saline in the same pattern. On the day before microdialysis, dialysis probes were lowered into the caudate putamen and nucleus accumbens. The next morning, after baseline dopamine collection, all animals received “binge” cocaine administration. Dialysates were collected every 20 min and dopamine content was determined by HPLC with electrochemical detection. In the basal condition, the mean level of dopamine in the dialysate from both brain regions of mice pretreated with “binge” pattern cocaine administration was significantly lower than that of the mice pretreated with saline administration. The absolute levels of dopamine achieved following “binge” pattern cocaine challenge were lower in the mice that had received chronic cocaine administration. However, when expressed as percent increase over baseline, the dopamine response to cocaine in the nucleus accumbens was significantly higher in mice that received chronic than in mice that received acute cocaine administration. Chronic cocaine administration led to a lowering of both basal dopamine and the absolute levels of cocaine‐induced increases of dopamine in the two brain regions, but enhanced the percent increases over the baseline in response to cocaine in the nucleus accumbens of both mouse strains. Synapse 50:191–199, 2003. © 2003 Wiley‐Liss, Inc.