Background Cholesterol lowering over 1- to 3-year trials is associated with modest regression or no progression of focal coronary artery stenoses compared with progression in controls, a decrease in cardiac events proportionately more than the modest improvement in percent stenosis, and in experimental animals improved endothelial-mediated coronary vasodilation.Methods and Results Accordingly, we hypothesized that there would be improvement in size and severity of perfusion abnormalities by rest-dipyridamole positron emission tomography (PET) imaging in a randomized intensive cholesterol-lowering trial with each patient studied after a baseline control period, a 90-day intensive cholesterol-lowering treatment, and a final control period off cholesterol-lowering regimens. Completely automated, objective measures of size and severity of perfusion abnormalities on rest-dipyridamole PET images were made by computer algorithm in 12 patients with coronary artery disease. There were statistically significant decreases (improvement) in size and severity of perfusion abnormalities by rest-dipyridamole PET on comparison of baseline control with perfusion abnormalities after intensive 90-day cholesterol lowering and significant increases (worsening) in size and severity after the final control period, respectively, as follows. (1) The percent of left ventricle outside 2.5 SD of normal values on the dipyridamole-to-rest ratio image of normalized counts was 22+-20% after the initial control period, 13+-14% after the treatment period, and 26+-22% after the final control period with a significant decrease (improvement) occurring between the initial control and treatment periods (P=.02) and an increase (worsening) occurring between the treatment and final control periods (P=.009). (2) The percent of left ventricle with a ratio of <=0.66 in the dipyridamole-to-rest ratio image of normalized counts was 11+-13% after the initial control period, 5.8+-10% after the treatment period, and 14+-19% after the final control period with a significant decrease (improvement) occurring between the initial control and treatment periods (P=.04) and an increase (worsening) occurring between the treatment and final control periods (P=.02). (3) The myocardial quadrant on the polar display with the lowest average activity expressed as a percent of maximal activity was 0.81+-0.18 after the initial control period, 0.87+-0.014 after the treatment period, and 0.77+-0.23 after the final control period with significant improvement occurring between the initial control and treatment periods (P=.05) and worsening occurring between the treatment and final control periods (P=.05).Conclusions These results suggest that relatively short-term, intensive cholesterol lowering over 90 days improves myocardial perfusion capacity before anatomic regression of stenoses occurs and that such improvement, or deterioration after withdrawal of lipid-lowering treatment, can be followed noninvasively by dipyridamole PET, reflecting the integrated flow capacity of the entire coronary arterial/arteriolar vascular system affected by diffuse atherosclerosis. (Circulation. 1994;89: 1530-1538.)