Male CD-strain rats (100--125 g) received fenitrothion by oral gavage (2.5, 5.0, 10.0 or 20.0 mg/kg/day) for 30 consecutive days. Control animals received equivalent volumes of taurocholate vehicle. Animals were killed at 8, 15, 22 and 30 days during treatment and at 8, 15, 29, 57 and 85 days after terminating treatment. The brain plasma and erythrocyte cholinesterases, hepatic and renal non-specific carboxylesterases were assayed. Serum biochemical markers of hepatic function were measured. Histologically stained sections of liver were examined by light microscopy. Fenitrothion, at doses between 2.5 and 10 mg/kg body wt, caused few observable deleterious effects to male rats except those effects on tissue esterases associated with organophosphorus esters. Only 8 of 36 animals receiving the 20.0 mg/kg dose died, all in the first week of treatment. A dose-dependent decrease in tissue esterase activity was observed which persisted throughout the entire treatment period. Periodic signs of overt toxicity were observed only in animals receiving 20 mg/kg/day. Tissue esterase activities returned to control levels within 1 or 2 weeks of stopping treatment. No significant treatment-related changes were observed by serum biochemistry or by light microscopy.