Tests of locomotor activity (photocell cages) were used to investigate the development of tolerance to nicotine in rats. Repeated exposure to the apparatus did not influence the rate at which tolerance was acquired. Comparisons of (+)-nicotine (0.4-1.6 mg kg-1, s.c.) and (-)-nicotine (0.1-0.4 mg kg-1, s.c.) in tolerant rats showed that the (-)-isomer was at least ten times more potent in stimulating motor activity. Subcutaneous pretreatment with mecamylamine (1.0 mg kg-1) completely prevented the locomotor stimulant action of nicotine in tolerant rats, whereas chlorisondamine (0.01 or 0.1 mg kg-1 s.c.) only partially reduced it. When mecamylamine was given after an injection of nicotine, the locomotor stimulant action of nicotine was blocked, and nicotine actually reduced activity. A single intraventricular dose of chlorisondamine (2 micrograms) blocked the stimulant actions of nicotine for the duration of the experiment (23-24 days).