The rat model is used to verify disulfiram-associated hypercholesterolemia and to determine a mechanism of action. Administration of disulfiram 15 mg/kg/day for 3 wk is associated with a 25% increase in serum cholesterol which is reversible with discontinuance of the drug. The hypercholesterolemia is due in part to a fourfold increase in activity of hepatic HMG-CoA reductase, the rate-limiting step in cholesterol biosyntheses.