The mechanisms for the lower toxicity of fenitrothion as compared with methylparathion were investigated in male rats. The difference in the acute toxicity of the insecticides could be the more rapid decomposition of fenitrothion and fenitrooxon in rat liver than that of methylparathion and methylparaoxon. In particular, the decomposition of fenitrothion by hepatic microsomes was accelerated by increasing the insecticide concentration as the substrate. The oxygen analogues of both insecticides, fenitrooxon and methylparaoxon, were not detected in the brain after the administration of their parent compounds. From these results, it is concluded that the lower toxicity of fenitrothion as compared with methylparathion could be due to the greater rate of the decomposition of fenitrothion to its less toxic metabolites, rather than to the relative rate of penetration of the oxygen analogues into brain.