We evaluated the effects of extracellular acidic conditions on glutamate-induced death in cultured retinal neurons. Primary retinal cultures, obtained from 3- to 5-day-old Wistar rats, were estimated to be consisted of mainly amacrine cells (90%) together with a small population of horizontal (8%) and ganglion cells (2%). We examined the effects of acidic pH (pH 6.0 to 7.0) on glutamate neurotoxicity by monitoring the delayed death of retinal neurons induced by brief (10 min) exposure to 1 mM glutamate followed by a 24-hr incubation. The glutamate-induced delayed death of cultured retinal neurons was attenuated with an acidic pH between 6.0 and 7.0. Furthermore, whole-cell patch-clamp recordings were taken from retinal neurons to examine the effects of acidic pH on N-methyl-D-aspartate (NMDA) or kainate receptor-mediated currents. NMDA- and kainate-induced currents were suppressed at pH 6.0 to 7.0 and pH 6.0 to 6.5, respectively. The acidity of the medium protected the retinal neurons from glutamate-induced delayed death, probably by inhibiting NMDA and/or kainate receptor activation.