When injected into the rat striatum, quinolinic acid causes dose-dependent widespread cell death. All cell types, including the NADPH-diaphorase-positive neurons appear to be sensitive to the toxin. The latter cells are destroyed by quinolinic acid injections of 180 nmol per striatum, this effect being blocked by the concomitant administration of 5 mg/kg of the non-competitive N-methyl-D-aspartate antagonist MK-801. We report that guanosine-5'-monophosphate (GMP), at a dose of 360 nmol, is equally effective in protecting the diaphorase-positive cells against quinolinate toxicity.