To test the hypothesis that physical inactivity is associated with increased stroke risk in women and men, the authors analyzed data from a longitudinal cohort study with three follow-up data collection waves. In the Nation Health and Nutrition Examination Survey I (NHANES I) Epidemiologic Follow-up Study, 7,895 white persons and black persons aged 45-74 years were examined in 1971-1975 as part of NHANES I. Included in this analysis were 5,852 persons without a history of stroke (fatal and nonfatal) or missing data. The average follow-up was 11.6 years (maximum, 16.4 years). Incident stroke (fatal or nonfatal) was the main outcome measure. Events were ascertained from cause of death information coded from death certificates and from discharge diagnoses coded from hospital and nursing home records during the follow-up period (1971 through 1987). Participants were asked to characterize their level of habitual physical activity as low, moderate, of high. The relative risk for stroke was estimated by Cox proportional hazards regression analysis, comparing persons reporting low with those reporting high physical activity at baseline and persons in the upper with those in the lower tertile of resting pulse rate. There were 249 incident cases of stroke identified in white women, 270 in white men, and 104 in blacks. In white women aged 65-74 years, low nonrecreational activity was associated with an increased risk of stroke (relative risk = 1.82,95% confidence interval 1.10-3.02) after adjusting for the baseline risk factors of age, smoking, history of diabetes, history of heart disease, education, systolic blood pressure, serum total cholesterol, body mass index, and hemoglobin concentration. Similar associations were seen for men and for blacks and for low recreational activity in women. A higher resting pulse rate was associated with an increased risk of stroke in blacks but not in whites. A consistent association of reported low physical activity with an increased risk of stroke was observed in white women. Regular physical activity may be of benefit in preventing stroke in women as well as men.