A cohort of 1,804 residents of Rochester, Minnesota, who were at least 50 years old, free of stroke, and who underwent examination at the Mayo Clinic in 1960, was followed for 13 years. During this period, there were 110 first ischemic strokes and 616 deaths without stroke. The time of onset, if available, or the time of diagnosis of potential risk factors was determined for all patients during the study and was used to construct a proportional hazards model of time to occurrence of stroke with time-dependent risk factors. The model included 8 risk factors (2 fixed and 6 time-dependent). For these, the individual relative risks are: 1.6 for age (per 10 years), 2.0 for males, 4.0 for definite hypertension, 3.9 for transient ischemic attacks, 2.2 for hypertensive heart disease, 2.2 for coronary heart disease, 1.7 for congestive heart failure, and 1.7 for diabetes mellitus. Atrial fibrillation was not a significant risk factor using time-dependent multivariate analysis.