Individuals with greater nicotine-reactivity may be more likely to initiate and maintain cigarette-smoking behavior than individuals with less nicotine-reactivity. In rats, behavioral sensitization reflects a progressive increase in the psychomotor response to drugs of abuse thought to result from neuroplasticity in brain regions that mediate their motivational effects. Studying nicotine behavioral sensitization in rats with differential nicotine preference and intake, such as Lewis and Fischer rats, may provide clues about the role of nicotine-reactivity in tobacco use. Rat strain differences in nicotine behavioral sensitization may contribute to strain differences in nicotine preference, sensitivity, and intake. In the present research, nicotine behavioral sensitization to multiple doses was examined in Lewis and Fischer rats. Subjects were 96 late adolescent male (48 Fischer, 48 Lewis) rats. Rats received subcutaneous injections of nicotine (0.2, 0.4, 0.7, 1.4, 2.8 mg/kg) or saline daily, and locomotor activity was measured immediately following injections on alternating days to examine sensitization. Behavioral sensitization occurred in both rat strains at the 0.2, 0.4, 0.7, and 1.4 mg/kg nicotine doses, but did not differ between Lewis and Fischer rats. The pattern of horizontal activity that occurred in response to the 2.8 mg/kg nicotine dose did not reflect behavioral sensitization. Results indicate that nicotine behavioral sensitization occurred in Lewis and Fischer rats, and did not differ between the two rat strains. It can be concluded that reported rat strain differences in nicotine intake, sensitivity, and preference do not result from rat strain differences in nicotine behavioral sensitization.