In the present study, we investigated the effects of histamine and its specific H-1, H-2 and H-3 receptor blockers in cerebellar granular cell culture derived from rat pups. Histamine was applied at 10(-9), 10(-8), 10(-7), 10(-6), and 10(-5) M for 16 h into the cultures and the highest dose was found to be the most toxic one. Pheniramine (H-1 receptor blocker), ranitidine (H-2 receptor blocker) and thioperamide (H-3 receptor blocker) were applied at 10(-8), 10(-7), 10(-6), 10(-5) M into the flasks prior to histamine in the second step of the experiments. Also, the effect of all of the blockers together at 10(-5) M concentrations was tested on the toxicity induced by 10(-5) M histamine. The H-3 receptor blocker, thioperamide (10(-6) M) was demonstrated to be most effective histamine toxicity blocker. Histamine H-2 blocker, ranitidine, was found to attenuate histamine neurotoxicity at all doses tested, its most effective dose being the highest dose. On the other hand, H-1 blocker, pheniramine, was able to reverse the effect of histamine at 10(-6) and 10(-5) M, but it was found ineffective when given at 10(-9) and 10(-8) M. Combined application of H-1, H-2, and H-3 receptor blockers at 10(-5) M concentrations, 45 min before histamine addition into the flasks at 10(-5) M, was able to reduce cell death score but it was not as effective as H-3 blocker, thioperamide.