The mechanism of the hypolipidemic action of bezafibrate was investigated in rats. Bezafibrate decreased the incorporation of 14C-acetic acid into the liver and serum triglyceride and inhibited liver acetyl CoA carboxylate activity. Bezafibrate increased liver beta-oxidation, but it had no effect on lipolysis and triglyceride secretion from the liver. Bezafibrate accelerated the elimination of serum triglyceride in Intralipid injected rats and increased tissue lipoprotein lipase activity. Bezafibrate decreased the incorporation of 14C-acetic acid into liver cholesterol and inhibited liver HMG-CoA reductase activity. Bezafibrate had no effect on cholesterol absorption and excretion. These results suggest that the hypotriglyceridemic actions of bezafibrate are due to inhibition of triglyceride synthesis and acceleration of triglyceride elimination and that the hypocholesterolemic action of bezafibrate is mainly due to inhibition of liver HMG-CoA reductase activity.