The Scandinavian Simvastatin Survival Study is a clinical trial of patients with coronary artery disease (CAD) and mild or moderate hypercholesterolemia. The primary objective is to investigate whether long-term treatment with the serum lipid-lowering agent simvastatin in patients with serum total cholesterol levels between 5.5 and 8.0 mmol/liter (212 to 309 mg/dl) will reduce overall mortality. The secondary objective is to investigate whether simvastatin treatment reduces the incidence of major CAD events (fatal and nonfatal myocardial infarction and sudden death). This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. Patients of both sexes, aged 35 to 69 years, with stable angina pectoris or previous myocardial infarction were recruited at 94 clinical centers throughout Scandinavia. Dietary advice was given to 7,027 patients who were followed for 2 months. Of these, 4,444 met the eligibility criteria and were subsequently randomized to receive simvastatin or similar placebo tablets. The patients will be followed for a minimum of 3 years and until total mortality reaches 440 deaths. This report presents certain design features of this study such as methods of recruitment and follow-up of patients, adjustment procedures for the test drug dose, sample size and power calculations, and organization of the study. Baseline results are summarized and ethical aspects of the study are also discussed.