Intermittent claudication, myocardial infarction, and angina pectoris share many epidemiologic and biologic features. Yet few large cohort studies describing the prevalence, incidence, and risk factors for intermittent claudication have been done. The authors evaluated intermittent claudication in 10,059 Israeli men aged 40-65 years, of whom 8,343 were free of coronary heart disease and symptoms of peripheral vascular disease; this latter group was followed for 5 years from 1963 to 1968. Prevalent and incident cases of intermittent claudication were defined by the London School of Hygiene Cardiovascular Disease Questionnaire, and all cardiovascular disease risk factor evaluations were standardized. Baseline prevalence was 27.0/1,000 (211/10,029). A total of 360 previously healthy men developed intermittent claudication for a crude 5-year incidence rate of 43.1/1,000 (360/8,343) or a crude annual incidence of 8.6/1,000. Following univariate analysis with demographic, physiologic, psychosocial, and other cardiovascular disease variables, logistic regression was used to identify risk factors for intermittent claudication. These were the following: > 20 cigarettes per day, odds ratio (OR) = 2.02, 95% confidence interval (CI) 1.54-2.66; serum cholesterol (50-mg/dl difference), OR = 1.35, 95% CI 1.18-1.54; 11-20 cigarettes per day, OR = 1.69, 95% CI 1.24-2.30; anxiety (high vs. low), OR = 1.85, 95% CI 1.29-2.65; socioeconomic status, OR = 1.82, 95% CI 1.26-2.64; and diabetes, OR = 1.85, 95% CI 1.25-2.75. Other significant predictors of smaller magnitude included in the regression were age, psychosocial coping factors, Quetelet's index, and exsmoking. The risk factors for intermittent claudication were a blend of those related to myocardial infarction (smoking, cholesterol, diabetes, but not hypertension) and others related to angina pectoris but not to myocardial infarction (stress and coping variables). There is reason to believe that preventing or modifying these factors will prove effective in altering the natural history and clinical outcomes of peripheral vascular disease as shown in other forms of atherosclerosis.