The effects of phenobarbital on the histology of the liver and the brain and on selected biochemical parameters of the liver of wistar rats were studied. Histological examination showed prominent lesions in the liver and brain of the tested groups of rats. Biochemical analysis revealed significant (P < 0.05) increase in the activities of alkaline phosphatase, alanine transaminase and in the level of cholesterol, with increased drug dosage. These correlated with the pathological changes observed in the liver and the brain of the wistar rats. The effects of phenobarbital on the liver and brain cells were found to be dose-dependent. Half the LD 50 of the drug (8mg/160g) administered on the rats caused reasonable injuries to the tissues of the liver and the brain of the wistar rats.