Strychnine-insensitive glycine receptors are known to modulate the toxicity of excitatory amino acids via an allosteric action at the N-methyl-D-aspartate receptor complex. To elucidate whether strychnine-sensitive glycine receptors may also influence excitotoxicity, the effect of strychnine on the excitotoxic cell death was examined in primary cultures of the rat cerebral cortex. To exclude any interference at the N-methyl-D-aspartate receptor complex, cell death was evoked by kainic acid. The release of lactic dehydrogenase (LDH) into the culture medium was taken as a quantitative measure of cell death. Strychnine reduced the excitotoxic cell death in a concentration-dependent fashion. This finding indicates that glycine may modulate the vulnerability of cortical cells to excitotoxic insults not only via the strychnine-insensitive population of glycine receptors within the N-methyl-D-aspartate receptor-complex, but also via strychnine-sensitive receptor channels.