The independent effect of exposure to environmental tobacco smoke (ETS; passive smoking) on the risk of stroke is not well established. We performed a cohort study among 27,698 lifelong nonsmokers with no prior history of stroke, 62% women, aged 30-85 years at enrollment (1979-1985). Self-reported ETS exposure at home and outside home (in hours/week) and stroke risk factors were collected at a health plan in San Francisco and Oakland. Follow-up for hospitalization and death was available through the end of 2000 (median = 16 years). In multivariate analysis adjusting for age, race/ethnicity, educational attainment, marital status, hypertension, diabetes and serum total cholesterol, ETS exposure at home of 20 h or more/week (in relation to <1 h/week) was associated with a 1.29-fold (95% CI 0.75-2.20) and a 1.50-fold (95% CI 1.07-2.09) increased risk of first ischemic stroke among men and women, respectively. No significant associations were found between ETS exposure outside home and ischemic stroke or between exposure to ETS at home or out of home and the risk of transient ischemic attack. Although potentially important confounders (such as dietary habits) were not included in the analysis, high-level ETS exposure at home was independently associated with increased risk of first ischemic stroke among never-smoking women.