The microiontophoretic application of dopamine onto neurons in the substantia nigra of rats increased the spontaneous activity of zona reticulata (ZR) neurons but decreased the activity of zone compacta (ZC) neurons. The systemic administration of the dopamine antagonists, haloperidol and cis-flupentixol, blocked the dopamine effects. However, haloperidol was more potent on ZC neurons that on ZR neurons whereas cis-flupentixol was of comparable potency on ZC and ZR neurons. In addition, microiontophoretic application of a cyclic adenosine monophosphate analog was found to mimic the effects of dopamine on ZR neurons, but not on ZC neurons. Taken together with receptor binding studies on the relative affinities of haloperidol and cis-flupentixol for various dopamine receptor subtypes, these data suggest that the excitatory effect of dopamine on ZR neurons is mediated by a D-1 type receptor whereas its inhibitory effect on the ZC dopaminergic neuron is mediated by a D-2 type receptor.