Although hyperuricemia is frequently found among persons with ischemic heart disease, its importance as a risk factor remains uncertain. The authors examined this relation among 5,421 persons in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study; baseline data were collected in 1971-1975 and follow-up was through 1987. No associations were seen among men, but, among women, the serum uric acid level was predictive of mortality from all causes and from ischemic heart disease. These associations persisted even after excluding the first 10 years of follow-up and were independent of use of antihypertensive agents and diuretics, diastolic blood pressure, overweight, and other characteristics. A dose-response relation was evident for mortality from ischemic heart disease: each 1-mg/dl change in uric acid (about two thirds of the standard deviation) among women increased the rate by 1.48 (95% confidence interval 1.3-1.7). Furthermore, as compared with women who had a uric acid level < 4 mg/dl, those with a level > or = 7 mg/dl had a 4.8-fold (95% confidence interval 1.9-12) higher rate of ischemic heart disease mortality. In contrast, the uric acid level showed a weaker relation with disease incidence among women, with a rate ratio of 1.14 for each 1-mg/dl change. Although the biologic mechanism is unclear, further investigation into the possible role of uric acid in the development of ischemic heart disease is needed.