We performed a cost-effectiveness analysis of pharmacologic treatment of high blood cholesterol levels. Agents modeled were cholestyramine, colestipol, gemfibrozil, lovastatin, niacin, and probucol. Pharmacologic effectiveness was estimated from reported studies. Cost estimates reflect societal resource consumption. Annual costs for therapy ranged from $327 (niacin) to $1881 (lovastatin, 80 mg/d). Niacin was the most efficient agent for reducing low-density lipoprotein cholesterol levels, having an average cost over 5 years of $139 per percent reduction in low-density lipoprotein cholesterol level. Lovastatin (20 mg/d) was also efficient ($177 per percent reduction). Cholestyramine was least efficient at $347. For high-density lipoprotein cholesterol, niacin was most efficient, at $116 per percent increase in high-density lipoprotein cholesterol level, followed by gemfibrozil at $271. Analyses combining low-density lipoprotein cholesterol and high-density lipoprotein cholesterol effects suggest that niacin and lovastatin (20 mg/d) were most efficient for reducing cardiovascular risk.