More than 90% of cigarette smokers begin smoking during adolescence, suggesting that adolescents may be particularly vulnerable to nicotine's effects. This experiment examined: (1) nicotine's acute effects on locomotion in adolescent and adult male Sprague-Dawley rats (Drug Phase I); (2) the effects of age of initial nicotine exposure on locomotion when nicotine was not administered (Interim Phase); and (3) the effects of age of initial nicotine exposure on later responses to nicotine (Drug Phase II). In Drug Phase I, animals were administered 0, 0.01, 0.10, 0.50, or 1.0 mg/kg nicotine sc for 12 days and horizontal activity was measured daily. During the Interim Phase, activity was measured but nicotine was not administered. During Drug Phase II, animals were administered the same nicotine dosages as in Drug Phase I for 12 days, and activity was measured daily. Drug Phase I revealed dose-response differences between adolescents and adults such that adolescents exhibited peak activity at both the 0.50- and 1.0-mg/kg dosages, but adults exhibited peak activity at the 0.50-mg/kg dosage. Initial nicotine exposure in adolescence (0.50 and 1.0 mg/kg), but not in adulthood, resulted in hyperactivity in adulthood in the absence of nicotine (Interim Phase). Reexposure to nicotine when all animals were adults (Drug Phase II) revealed that initial nicotine exposure in adolescence compared to adulthood resulted in dose-response differences in adulthood similar to those in Drug Phase I. In addition, animals initially exposed in adolescence exhibited sensitization to nicotine's activity-increasing effects in adulthood. These findings suggest that there are age differences in nicotine sensitivity that could predispose individuals initially exposed to nicotine in adolescence to long-term smoking.