LIPID is a multicenter, double-blind, randomized, placebo-controlled trial comparing the effects of pravastatin, 40 mg/day, with placebo, given for > or = 5 years, in patients aged 31 to 75 years with a total cholesterol level at baseline of 4.0 to 7.0 mmol/L (155 to 270 mg/dl), and with a history of acute myocardial infarction (AMI) or hospitalization for unstable angina pectoris (UAP). Each group receives dietary advice according to National Heart Foundation guidelines. Individual care of each patient is otherwise left to the discretion of the patient's usual doctor. The study has a primary outcome of coronary mortality, and is designed to detect an 18% reduction with 80% power. From April 1990 to September 1992, 11,106 patients were registered, and following the run-in phase, 9,014 were randomized: 5,754 (64%) after a qualifying event of AMI and 3,260 (36%) after hospitalization for UAP. The randomized population includes relatively large numbers in subgroups not assessed reliably in earlier trials: 1,511 women, 3,516 patients aged > or = 65 years, 777 diabetics, and 3,829 patients with serum cholesterol < or = 5.5 mmol/L (213 mg/dl) at baseline. With a projected 700 fatal coronary events, the trial should be able to detect important reductions in coronary mortality and contribute substantially to prospective meta-analyses to detect effects on total mortality. The spectrum of patients being assessed will improve the reliability of evidence for the benefits and risks of cholesterol-lowering therapies in patients with lower cholesterol levels and in other important subgroups.