Repeated treatment with nicotine has been shown to sensitize rats to its locomotor stimulant effects and to its properties to stimulate mesolimbic dopamine transmission. We investigated the relationship between sensitization of nicotine induced locomotor stimulation and activation of dopamine transmission in the nucleus accumbens shell and core. Rats were administered daily for 5 days with 0.4 mg/kg s.c. of nicotine or with saline and 24 h later, dopamine was monitored by microdialysis in the shell and in the core of nucleus accumbens and behavioral activity was scored after challenge with nicotine (0. 4 mg/kg s.c.). Behavioral sensitization to nicotine was associated with a reduced response of dopamine transmission in the shell and with an increased one in the core of nucleus accumbens.