Extracellular recordings of single unit activity were made in the substantia nigra (SN) of chloral hydrate-anaesthetized rats. Dopaminergic neurones of the pars compacta (SNC) were stimulated by (-)-nicotine bitartrate (1.0 mg kg-1) given subcutaneously (s.c.). This action was prevented by the secondary amine mecamylamine HCl (2.0 mg kg-1 i.v.) but not by a ganglion-blocking dose of the bisquaternary compound chlorisondamine Cl (0.1 mg kg-1 i.v.). Mecamylamine reduced the spontaneous activity of dopaminergic neurones. Nicotine, when administered intravenously (2-128 micrograms kg-1 cumulative dose), also stimulated dopamine cells and this action was dose-related. Nicotine, administered intravenously, (2-128 micrograms kg-1 cumulative dose) markedly excited non-dopamine cells in the pars reticulata (SNR) in a dose-related manner. In rats pretreated with chlorisondamine (0.1 mg kg-1 i.v.), nicotine induced a small excitatory or depressant action, but the marked excitation was not seen. Mecamylamine (2 mg kg-1 i.v.) completely prevented the actions of nicotine. The results are consistent with a direct excitatory action of nicotine on dopaminergic neurones of the substantia nigra pars compacta. The pronounced excitatory action of systemically administered nicotine on non-dopamine cells of the pars reticulata appears to be of peripheral origin.