The response of two populations of neurones in the substantia nigra (nigro-striatal compacta neurones and reticulata neurones) to microelectrophoretically administered putative neurotransmitters and stimulation of the ipsilateral striatum has been investigated in anaesthetized rats. There were marked differences between compacta and reticulata neurones in respect to their action potential configurations, spontaneous firing rates and their responses to striatal stimulation. However, both compacta and reticulata neurones were excited and/or inhibited by striatal stimulation, although inhibition was usually the predominant response in both neuronal populations. Compacta neurones were strongly inhibited by noradrenaline (NA) and dopamine (DA) but were unaffected by acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). Reticulata neurones were excited by ACh and showed mixed responses to 5-HT, DA and NA. Excitant amino acids overdepolarized compacta neurones preventing them from firing rapidly, but induced large increases in reticulata neurone firing rate; effects that were readily antagonized by D-alpha-aminoadipate. Compacta neurones were less sensitive than reticulata neurones to GABA and glycine. The action of these inhibitory amino acids were selectively and reversibly antagonized by bicuculline methochloride and strychnine, respectively. The striatal-evoked inhibition of both compacta and reticulata neurones was reversibly reduced by bicuculline methochloride and irreversibly reduced by tetanus toxin, but was unaffected by strychnine. These results demonstrate that nigrostriatal-compacta neurones and reticulata neurones are physiologically and pharmacologically distinct neuronal populations and both receive inhibitory GABAergic and excitatory striatal inputs.