The NMDA regulation of the dendritic release of [3H]dopamine ([3H]DA) synthesized from [3H]tyrosine was investigated in vitro using a microsuperfusion procedure in the pars compacta (SNC) and the pars reticulata (SNR) of the cat substantia nigra. The spontaneous release of [3H]DA was threefold higher in the SNC than in the SNR and amphetamine (1 microM) enhanced similarly [3H]DA release in both nigral areas. In the absence of magnesium, NMDA (50 microM) stimulated markedly the release of [3H]DA in the SNC and SNR, these effects being completely prevented by MK 801 (1 microM), the NMDA receptor antagonist. The DA uptake inhibitor, nomifensine (5 microM), increased the amount of [3H]DA recovered in SNC (x2) and SNR (x3) superfusates but did not significantly modify the NMDA-evoked responses. The effects of NMDA seen in the absence or presence of nomifensine persisted when the two nigral areas were continuously superfused with tetrodotoxin (1 microM). These results are in favor of the presence of NMDA receptors on dopaminergic dendritic arborizations and indicate that the stimulation of these receptors facilitates in a similar way the release of DA from proximal and distal dendrites.