OBJECTIVE: To determine if the association between smoking and osteoporotic fractures is related to the quantity of cigarettes smoked and to determine if smoking modifies the protection by estrogens. DESIGN: Cohort study. SETTING: A population-based cohort study, the Framingham Study. PARTICIPANTS: A total of 2873 women in the Framingham Study followed through examination 19 (1985-1987). MEASUREMENTS: All fractures of the proximal femur sustained by women in the Framingham Study from 1948 to 1987 were ascertained. At almost all examinations, available information on cigarette smoking was used to classify women as "ever smokers" compared with "never smokers," and, among "ever smokers," "current" compared with "former smokers." A similar classification for estrogen use was created. Information on potentially confounding variables was taken from each examination, including age, adiposity (weight/height2), alcohol consumption (ounces per week), and caffeine intake (coffee and tea). RESULTS: Overall, 207 hip fractures occurred among 34,700 woman-examinations of observation. In the entire cohort, current smoking did not appear to increase hip fracture risk (adjusted odds ratio [AOR], 1.22; 95% CI, 0.76 to 1.95; P greater than 0.2). Also overall, current estrogen use appeared to be protective (AOR, 0.38; CI, 0.12 to 1.21, P = 0.10). Among current smokers, however, estrogen use did not protect against fracture (AOR for current use, 1.26; CI, 0.29 to 5.45), whereas estrogen was protective in nonsmokers (AOR for current or past use, 0.37; CI, 0.19 to 0.75; P = 0.005). CONCLUSIONS: Overall, smoking does not appear to increase the risk for hip fracture in women. Although estrogen replacement protects nonsmokers from fracture, smoking may negate the protective skeletal effects of estrogen replacement therapy.