Intracellular and extracellular recordings were obtained from ganglion cells in the rabbit retina. The effect of N-methyl-DL-aspartate (NMDLA) and N-methyl-D-aspartate (NMDA) antagonists were studied with the use of a perfusion method for drug application. NMDLA exicted all ganglion cell types and caused a characteristic burst firing pattern, which is not typical of physiological responses in the retina. When synaptic transmission was blocked with cobalt, NMDLA still excited ganglion cells, indicating a direct action. A comparison of DL-2-amino-5-phosphonopentanoate (DL-AP-5) and DL-2-amino-7-phosphonoheptanoate (DL-AP-7) revealed that DL-AP-7 was a more specific NMDA antagonist. DL-AP-5 partially blocked the b-wave of the electroretinogram (ERG), an action typical of L-2-amino-4-phosphonobutyrate (L-APB), which specifically blocks ON channels in the retina. DL-AP-7 reversibly blocked the action of NMDLA on all ganglion cell types, but the effects of kainate (KA) and carbachol were unchanged. AP-7 was stereospecific and pharmacologically specific, with action typical of a competitive NMDA antagonist in the rabbit retina. DL-AP-7 did not block light responses driven by center or surround stimulation for ON or OFF ganglion cells. Directional selectivity was unchanged by DL-AP-7. However, most ganglion cells showed a reduction, typically 20-30%, in the number of action potentials produced by light stimulation. In contrast to a previous report, we found no evidence that DL-AP-7 specifically inhibited sustained ON ganglion cells. The inhibition of sustained ON responses by DL-AP-5, previously attributed to NMDA antagonism, is probably because of the weak APB activity of L-AP-5. We conclude that NMDA receptors do not mediate the major light-drive input to ganglion cells in the rabbit retina. By exclusion, transmission from bipolar cells to ganglion cells appears to be carried mostly by KA or quisqualate (QQ) receptors. However, because NMDA antagonists reduced the number of action potentials produced by light stimulation, it is likely that NMDA receptors carry a portion of the signal transmission to ganglion cells. The presence of NMDA receptors on third-order neurons is consistent with the release of glutamate from presynaptic neurons such as bipolar cells.