1--Rats were tested for locomotor activity in photocell cages, for 80 min starting immediately after subcutaneous injection of (-)-nicotine bitartrate or 0.9% w/v NaCl solution (saline). In non-tolerant subjects, nicotine (0.1 to 0.4 mg/kg base) depressed activity and induced ataxia in the first 20 min, but increased activity later in the session; these actions were dose-dependent. 2--Tolerance was studied by comparing rats given nicotine (0.4 mg/kg s.c.) every day with control rats given saline instead. Each week, every subject was tested once with nicotine (0.4 mg/kg) and once with saline. With daily or even weekly injections of nicotine, the initial depressant action of the drug was replaced by a dose-dependent stimulant action which occurred throughout the session. In these tolerant animals, little ataxia was seen except when a larger dose of 0.8 mg/kg was given. Tolerance to the depressant action of nicotine persisted for at least 3 weeks. 3--In non-tolerant subjects, mecamylamine (0.5, 1.0 mg/kg s.c.) prevented the initial depressant action of nicotine (0.4 mg/kg). In tolerant rats, the locomotor stimulant action of nicotine (0.4 mg/kg) was prevented by mecamylamine (0.1, 0.32, 1.0 mg/kg s.c.) in a dose-related way; the quaternary ganglion blocker, hexamethonium (0.2, 1.0, 5.0 mg/kg s.c.) had little or no such effect. Neither mecamylamine nor hexamethonium altered activity when given alone. 4--It is suggested that a few treatments with nicotine can unmask a stimulant action of the drug, probably of central origin, which possibly reflects a stimulation of nicotine receptors.