Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged ⩽ 70 years, all of whom had previously undergone coronary bypass surgery, were randomly assigned to receive either slow-release gemfibrozil, 1200 mg once daily, or a matching placebo for on average 2 1 2 years. The lipid inclusion criteria were HDL cholesterol concentration ⩽ 1.1mmol/L, low density lipoprotein (LDL) cholesterol ⩽ 4.5 mmol/L, and serum triglyceride ⩽ 4.0 mmol/L. Subjects were not accepted if they had manifest diabetes, body mass index > 30 kg/m2, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement System, a validated computer-assisted image-analysis and quantitation package. The primary endpoints are the changes in the per-patient mean of 1) the average diameter of evaluable native coronary segments, and 2) the minimal luminal diameter of evaluable stenoses, and 3) the appearance of new lesions. Extensive lipoprotein and other metabolic studies and analyses of genetic polymorphisms are carried out to study the determinants of CAD progression. At baseline, the study subjects were 59.1 ± 6.8 (mean ± standard deviation) years old, had a body mass index 26.4 ± 2.2 kg/m2, and serum triglyceride, serum cholesterol, HDL cholesterol, and LDL cholesterol concentrations 1.64 ± 0.64, 5.17 ± 0.64, 0.82 ± 0.14, and 3.61 ± 0.53 mmol/L, respectively.