Rats were trained to discriminate 200 or 400 microgram/kg (-)nicotine from saline in a two-bar operant paradigm. Dose-response relationships for optically pure (-)- and (+)nicotine as well as antagonistic effects were examined in both groups of rats. The natural isomer (-)nicotine was approximately nine-times more potent than (+)nicotine. Mecamylamine produced equal blockade of the (-)- and (+)nicotine cues. Hexamethonium and atropine were without effect. These data demonstrate the possible stereospecificity of the central nicotinic receptor that mediates the stimulus effect produced by nicotine.