The effects of a potent HMG CoA reductase inhibitor, lovastatin, was studied in male Syrian Golden hamsters. Lovastatin (0.1% in food for 6 days) increased hamster serum triglycerides by 12-fold with 2.4-fold increase in serum cholesterol. On continuous treatment serum triglyceride and cholesterol levels gradually decreased to below control values by 12-18 days. When hamsters were fed a mixture of lovastatin and Na-mevalonate no increase in serum triglyceride was observed. [14C]Cholesterol synthesis was increased by 266-fold in livers of hamsters fed lovastatin for 6 days. The increased synthesis of endogenous mevalonate metabolites may be a reason for the decrease in triglyceride levels after 6 days in our studies. The present study suggests that a mevalonate metabolite(s) is necessary for normal triglyceride metabolism in hamsters.