(NIDDM). Design.\p=m-\Prospective cohort study including 5 years of follow-up. Participants.\p=m-\21271 US male physicians participating in the Physicians' Health Study, aged 40 to 84 years and free of diagnosed diabetes mellitus, myo- cardial infarction, cerebrovascular disease, and cancer at baseline. Morbidity follow-up was 99.7% complete. Main Outcome Measure.\p=m-\Incidenceof NIDDM. Results.\p=m-\Atbaseline, information was obtained about frequency of vigorous exercise and other risk indicators. During 105141 person-years of follow-up, 285 new cases of NIDDM were reported. The age-adjusted incidence of NIDDM ranged from 369 cases per 100 000 person-years in men who engaged in vigorous exer- cise less than once weekly to 214 cases per 100000 person-years in those exer- cising at least five times per week (P, trend, <.001). Men who exercised at least once per week had an age-adjusted relative risk (RR) of NIDDM of 0.64 (95% Cl, 0.51 to 0.82; P=.0003) compared with those who exercised less frequently. The age-adjusted RR of NIDDM decreased with increasing frequency of exercise: 0.77 for once weekly, 0.62 for two to four times per week, and 0.58 for five or more times per week (P, trend, .0002). A significant reduction in risk of NIDDM persisted after adjustment for both age and body-mass index: RR, 0.71 (95% Cl, 0.56 to 0.91; P=.006) for at least once per week compared with less than once weekly, and P, trend, .009, for increasing frequency of exercise. Further control for smoking, hy- pertension, and other coronary risk factors did not materially alter these associa- tions. The inverse relation of exercise to risk of NIDDM was particularly pronounced among overweight men. Conclusions.\p=m-\Exerciseappears to reduce the development of NIDDM even after adjusting for body-mass index. Increased physical activity may be a promis- ing approach to the primary prevention of NIDDM.