Mortality in relation to relative weight and exercise was analyzed from data collected in the first 2 years of the American Cancer Society's Cancer Prevention Study II. It included data on 868,620 persons who had no history of cancer, heart disease, or stroke and who were not sick at the start of the study. Standardized mortality ratios (SMR) were 187 for men who were 20% or more underweight and 187 for men who were 40% or more overweight. Comparable SMR in women were 186 and 178. Current smokers had considerably higher SMR than nonsmokers for all causes of death and cancer deaths at each relative weight category. Degree of exercise reported by subjects was inversely related to mortality, independent of smoking habits. Subjects who exercised heavily and died of cancer of the lung, colon-rectum, and pancreas had 20% to 37% higher SMR than men and women who reported moderate exercise.