During 26 years of surveillance of the Framingham Study Cohort of 5,209 subjects, 176 men and 119 women developed occlusive peripheral arterial disease manifested as intermittent claudication (IC). The incidence increased sharply with age until the age of 75, with about a twofold male predominance at all ages. An incidence of IC comparable to that of angina pectoris was obtained ten years later in life than for angina pectoris. Cigarette smoking, impaired glucose tolerance, and hypertension were powerful predisposing factors. Impaired glucose tolerance was a greater risk in women than in men, and glycosuria carried a greater risk than other indicators of impaired glucose tolerance. Cigarette smoking had about the same impact in men and women, approximately doubling the risk, and the impact was discernible into advanced age. Hypertension increased risk 2.5- to fourfold, respectively, in men and women. A low vital capacity was associated with a substantial excess risk. Electrocardiographic evidence of left ventricular hypertrophy predicted IC in both sexes. Serum cholesterol, relative weight, and hematocrit were weak risk factors. A risk profile made up of the major cardiovascular risk factors was better for predicting IC than for predicting coronary heart disease. Mortality was increased two- to fourfold in men and women, respectively, mainly because of coexistent cardiovascular disease.