The effects of sodium nitroprusside (SNP) in rat cerebellar granular cell culture were investigated in the present study. All doses of the SNP (10, 25, 50, 100, 250, 500,muM) were able to induce cell death compared with control values (p<0.001 for all groups tested). Interestingly enough, a nonlinear dose-response curve was obtained for SNP-induced neurotoxicity. We also investigated the possible neuroprotective effects of nimodipine and dantrolene, alone or in combination. Both drugs failed to prevent neuronal cell death at the doses tested, either alone or in combination. Despite the fact that the most effective dose was a dantrolene concentration of 10 muM with SNP 500muM and a concentration of 1 mum with SNP 50 muM, the differences were insignificant statistically. According to our results, SNP-induced cerebellar toxicity appears to be an independent reaction from L-type or endoplasmic reticulum calcium currents.