The effects of nimodipine, an L-type calcium channel antagonist, on nicotine-induced locomotor activity were investigated in drug-naive rats. Nicotine (0.4 mg/kg i.p.) produced significant increases in locomotion following acute administration. However, when rats were given injections of nimodipine (5, 10, or 20 mg/kg i.p.) 1 h prior to the test drug, nicotine-induced locomotor activity was altered. Nimodipine 5 mg did not significantly block locomotor activity produced by nicotine. In contrast, pretreatment with 10 and 20 mg nimodipine significantly blocked nicotine-induced locomotor activity. These findings clearly indicate that nicotine-induced locomotion is altered by nimodipine in a dose-dependent fashion. Results further suggest that the effect of nicotine on locomotion is calcium-dependent.