This study is an investigation at the single neurone level of the pharmacology and afferent connections of the rat substantia nigra. In urethane, anaesthetised rats multibarrel glass micropipettes were used to record extracellular single unit activity and for the iontophoretic application of drugs. Concentric bipolar electrodes were used for the electrical stimulation of substantia nigra afferents. Iontophoretic application of substance P strongly excited substantia nigra neurones supporting its role as the excitatory transmitter in the striatonigral pathway. Leucine-enkephalin and D-serine2-methionineenkephalin were powerful depressants. f of nigral neurone activity while methionine-enkephalin was, less potent. Morphine had only excitatory effects in the substantia nigra. These results are explained in terns of different 'opiate' receptors. Bradykinin, neurotensin and angiotensin were all without effect when iontophoretically applied to sub stantia nigra neurones. Dopamine and noradrenaline had both excitatory and inhibitory effects on nigral neurones but the lack of correlation between their effects on the same cells suggests an action at separate receptors. 5-hydroxytryptamine also excited and inhibited substantia nigra neurones, the predominant effect being excitatory. Acetylcholine strongly excited a large percentage of substantia nigra neurones, though some were inhibited. Evidence from other cholinergic agonists and antagonists suggests that the excitations are both muscarinic and nicotinic while the inhibitions were muscarinic. The levels of amino acids within the substantia nigra were measured and those present in large amounts were iontophoretically applied to substantia nigra neurones. While baclofen inhibits nigral neurones it is unlikely to be by an action on GAGA receptors as its effects are not antagonised by picrotoxin. Evidence from electrical stimulation of the nucleus accumbens suggests that this nucleus can influence substantia nigra activity in a number of ways and that its direct effect is mainly through an inhibitory, possibly GABAergic, projection.