Clofibrate was administered in the diet (0.3% w/w) for varying periods of time to normal rats. Rats were killed by decapitation and several biochemical measurements were made. Clofibrate lowered serum levels of cholesterol and triglyceride and produced a kidney hypertrophy; these effects were maximal after 3 days of feeding and persisted for 21 days. Serum clofibric acid levels were highest on the 3rd day and decreased to maintenance levels by the 7th day. Clofibrate markedly increased the activities of glucose 6-phosphatase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase in kidney cortex and the synthesis of glucose from glutamate, lactate, pyruvate, glycerol and malate by kidney cortex slices. Clofibrate treatment did not affect blood pH or bicarbonate levels. It is concluded that clofibrate enhances renal gluconeogenesis in the rat and that the effect is not caused by altering acid-base balance.