The metabolism of isopropyl parathion was examined in the housefly, honey bee, and white mouse. Houseflies and honey bees metabolized isopropyl parathion in a qualitatively similar manner. The only water-soluble degradation product isolated and identified in the housefly and honey bee was O,O-diisopropyl phosphorothioic acid. Other metabolites appeared to be present in minor quantities but were not identified. Quantitatively, higher levels of organic-soluble material and, in particular, isopropyl paraoxon were found in the housefly than in the honey bee soon after treatment with isopropyl parathion. This, with the greater sensitivity of housefly cholinesterase to isopropyl paraoxon, explains the much greater toxicity of isopropyl parathion to the housefly than to the honey bee. The metabolism of isopropyl parathion in the white mouse was more complex than in the two insects. In addition to isopropyl paraoxon and diisopropyl phosphorothioic acid, evidence indicated the presence of O-isopropyl O-H O-4-nitrophenyl phosphorothioate and phosphate as major metabolites. © 1969, American Chemical Society. All rights reserved.