The effects of chronic gestational exposure to nicotine on the nucleus accumbens dopamine response to acute nicotine were determined during adolescence (postnatal day 29-36) in cross-fostered and noncross-fostered Lewis rats. In both males and females, gestational nicotine exposure diminished the adolescent nucleus accumbens dopamine response to 0.07 mg/kg nicotine i.v. (p < 0.05). However, dopamine responses to 0.105 mg/kg nicotine were unaffected by gestational nicotine treatment and were similar in both genders. Furthermore, in both female and male gestational nicotine and control groups, the dopamine response to nicotine (0.105) was the same as that observed to the lower dose of nicotine in gestational controls. Thus, in adolescent male and female Lewis rats, gestational nicotine exposure attenuated nucleus accumbens dopamine release to a maximally stimulative dose of nicotine. Unexpectedly, in female gestational controls cross-fostering per se reduced nucleus accumbens dopamine secretion to 0.07 mg/kg nicotine (p < 0.05). These investigations suggest that gestational nicotine exposure could modify the acute reinforcing effects of nicotine in adolescent rats, whereas early postnatal stressors, (e.g., cross-fostering) may affect nicotine-induced reinforcement in female but not male adolescents.