Relatively high serum albumin levels have been associated with reduced cardiovascular mortality and coronary heart disease incidence. No prospective studies have examined serum albumin and stroke mortality and incidence. Therefore, data from the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study were examined to assess serum albumin level as a risk factor for stroke. White men aged 65-74 years with serum albumin concentrations of > 4.4 g/dl had a risk of stroke incidence over a follow-up period of 9-16 years of only about two-thirds that of men with serum albumin concentrations of < 4.2 g/dl. This effect persisted after controlling for multiple stroke risk variables (relative risk = 0.61, 95% confidence interval 0.41-0.89). A similar association with stroke death was found in white men aged 65-74 years. Serum albumin was not associated with stroke risk in white women aged 65-74 years. In blacks aged 45-74 years, serum albumin concentrations of > 4.4 g/dl were associated with a risk of stroke incidence only one-half and a risk of stroke death only one-fourth that seen at levels < 4.2 g/dl after controlling other risk variables. Further studies are needed to confirm these findings and to elucidate mechanisms for the effect of serum albumin on stroke incidence and death.