Abstract The selective destruction of neuronal perikarya via intracerebral injections of kainic acid was used to elucidate the cellular location of four neurotransmitter-related enzymes in the substantia nigra (SN). Two weeks after intranigral injections of kainic acid, dopamine-sensitive adenylate cyclase, glutamic acid decar☐ylase (GAD), choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were measured in the SN. Histological examination of the SN, and a reduction of striatal tyrosine hydroxylase (TH) activity by 94%, confirmed the extensive loss of neuronal cell bodies in the SN. Dopamine stimulation of adenylate cyclase was not reduced in the lesioned SN, supporting the view that dendritically-released dopamine can regulate cyclic AMP synthesis in afferent terminals to these dendrites. Nigral GAD activity was significantly reduced by the lesions, suggesting that there are GAD-containing perikarya in the SN. CAT activity was not affected by the kainic injections, indicating the absence of cholinergic perikarya in the SN. Nigral AChE activity was significantly decreased after kainic injections, thus confirming the presence of AChE within the nigral perikarya. The results suggest that dopamine-sensitive adenylate cyclase and CAT are located within afferents to the SN, while GAD and AChE are found, to some extent at least, in neuronal soma of the SN. The differential effects of kainic acid on these enzymes suggest that this compound may be a useful neurochemical tool with which to determine the cellular distribution of enzyme systems in the central nervous system.