Rats and chickens were given single oral doses of 50 mg chlorpyrifos/kg to compare toxic effects in these 2 species. Oral administration resulted in decreased cytochrome P-450 and aminopyrine N-demethylase activities and increased cytosolic glutathione S-transferase activity in rats. On the contrary, there was increased cytochrome P-450 and aminopyrine N-demethylase activities in chickens. A significantly higher inhibition of serum cholinesterase (82%) was noted in rats than in chickens (55%). Serum gamma-glutamyl transferase, a marker of hepatotoxicity, remained unchanged in both species, indicating the absence of hepatotoxicity. These studies project chlorpyrifos to be an inhibitor of hepatic microsomal drug-metabolizing enzymes in rats and an inducer in chickens, and a non-hepatotoxic organophosphate insecticide in both species when given at the dosage of 50 mg/kg.