We examined the relation between the serum total cholesterol level and the risk of death from stroke during six years of follow-up in 350,977 men, 35 to 57 years of age, who had no history of heart attack and were not currently being treated for diabetes mellitus. The diagnosis of stroke and the type of stroke were obtained from death certificates. Using proportional-hazards regression to control for age, cigarette smoking, diastolic blood pressure, and race or ethnic group, we found that the six-year risk of death from Intracranial hemorrhage (International Classification of Diseases, ninth edition [ICD-9], categories 431 and 432) was three times higher in men with serum cholesterol levels under 4.14 mmol per liter (160 mg per deciliter) than in those with higher cholesterol levels (P = 0.05 by omnibus test across five cholesterol levels). On the other hand, a positive association was observed between the serum cholesterol level and death from nonhemorrhagic stroke (P = 0.007). The inverse association of the serum cholesterol level with the risk of death from intracranial hemorrhage was confined to men with diastolic blood pressure Ã¢â€°Â¥90 mm Hg, in whom death from intracranial hemorrhage is relatively common. We conclude that there is an inverse relation between the serum cholesterol level and the risk of death from hemorrhagic stroke in middle-aged American men, but that its public health impact is overwhelmed by the positive association of higher serum cholesterol levels with death from nonhemorrhagic stroke and total cardiovascular disease (ICD-9 categories 390 through 459). (N Engl J Med 1989; 320:904-10.) ALTHOUGH the relation of the serum level of total cholesterol to coronary heart disease is well established,1 2 3 4 its relation to stroke is less clear.5 6 7 8 9 10 11 Prospective studies of Japanese patients in Japan and of Japanese-American men in the Honolulu Heart Study indicate an inverse association of the serum cholesterol level with the occurrence of intracerebral hemorrhage and no significant relation of serum cholesterol to the risk of cerebral infarction.5 6 7 8 U.S. data show no significant association with all types of stroke or cerebral infarction.9 10 11 12 We know of no U.S. studies that have reported on the relation between serum cholesterol and cerebral hemorrhage.