Fifty-seven patients who had a significant (50) narrowing of a nongrafted coronary artery and a baseline cholesterol level >250 mg/dl were studied. All patients underwent repeat coronary arteriography after two years. Thirty-six colestipol responders (cholesterol levels reduced at least 15 within one month of therapy) were compared to 21 nonre-sponders who were given placeo for 23 months after a one-month exposure to colestipol. Baseline risk factors and demographic characteristics were similar for the two groups. In comparison to baseline arteriography, six of the 36 drug-treated patients showed progression of atherosclerosis, whereas ten of 21 placebo-treated patients demonstrated progression (P <.02). Drug-treated patients demonstrated an average 21 decrease in cholesterol levels, whereas placebo patients did not experience a significant reduction in cholesterol levels. Our study suggests that a significant reduction (15) in serum cholesterol level is associated with a reduced likelihood of progression of coronary atherosclerotic lesions assessed by scheduled repetitive coronary arteriography in hyperlipidemic subjects who demonstrate significant coronary artery narrowing.