Effects of a nitric oxide (NO)-producing agent, sodium nitroprusside, on N-methyl-D-aspartate (NMDA) receptor activation in the cultured retinal neurons of rats were examined. NMDA in a Mg(2+)-free medium evoked inward currents at the resting membrane potential. Inward currents were also evoked by kainate. Sodium nitroprusside markedly reduced the NMDA-induced currents without affecting those induced by kainate. These results suggest the possible existence of a negative feed back system of NO which serves to regulate the activation of NMDA receptors in retinal neurons.