Glutamate (10(-7) M) and one of its non-NMDA receptor agonists, kainic acid (10(-4) M), were administered to rat cerebellar granular cell cultures, and the neuroprotective role of salicylic acid was examined. Glutamate induced 38.58 +/- 1.45% neuronal cell death while kainic acid induced only 21.4 +/- 2.01% despite being 1000 times more concentrated. The most effective dose for the neuroprotective effect of salicylate in glutamate-induced neurotoxicity was 10(-5) M and it had no protective effect at 10(-7) M. With kainic acid-induced toxicity, 10(-6) M salicylate had no protective effect but 10(-5) M and 10(-4) M salicylic acid were very effective against kainic acid-induced toxicity. As an OH-trapping agent, salicylate had a protective role in NMDA and non-NMDA receptor-activated neuronal cell death. The present study gives some important clues about oxygen free radical generation having an important role in glutamate- and kainic acid-induced neurotoxicity. On the other hand, the neuroprotective effects of salicylic acid in the present study may depend on the pH alterations in salicylic acid solutions. (C) 2000 Academic Press.