We studied the effects of simvastatin (MK 733), a new competitive inhibitor of HMG CoA reductase, alone and in combination with a bile acid sequestrant, cholestyramine, on serum levels of lipoproteins and apoproteins A1 and B, in 24 patients with familial hypercholesterolemia. After simvastatin treatment (40 mg/day) alone for 12 weeks, serum total and low density lipoprotein cholesterol decreased by 31 and 36 percent respectively. With the addition of cholestyramine, there was a 41 per cent total decrease in serum cholesterol from the control value and a 50 percent decrease in low density lipoprotein cholesterol. After cholestyramine treatment alone for 12 weeks, serum total and low density lipoprotein cholesterol decreased by 20 percent and 29 percent respectively. With the addition of simvastatin (20 mg per day), there was a 32 percent total decrease in serum cholesterol from the control value and a 43 percent decrease in low density lipoprotein cholesterol. High density lipoprotein cholesterol remained unchanged. No major adverse effect was observed. If long term safety can be confirmed, the simvastatin-cholestyramine regimen may prove useful in heterozygous familial hypercholesterolemia.