Parathion toxicity has been attributed to its metabolic product paraoxon which is formed in the mammal liver through the multiple oxidase enzymes. These are induced by barbiturates and inhibited by SKF 525 A and cimetidine. We assessed the effects of these drugs on the acute toxicity of parathion in rats by measuring the rate of survival at 24 h after the administration of the oral LD50 of parathion to four groups of rats: control and pretreated with the aforementioned drugs. Additional rats of these groups were used to measure the capability of liver isolated microsomes to transform p-nitroanisole to p-nitrophenol. In the control and cimetidine groups we also measured the transformation of parathion to paraoxon and p-nitrophenol by the liver microsomes. Phenobarbital increased the survival 100% whereas cimetidine and SKF 525 A dramatically potentiated parathion toxicity. Phenobarbital increased the formation of p-nitrophenol but cimetidine and SKF-525 A produced the opposite effect. Paraoxon and p-nitrophenol from parathion were decreased by cimetidine. Our results strongly suggest that parathion itself is largely responsible of its toxicity and the inhibition of its metabolism is harmful rather than beneficial.