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The authors examined the association between dietary intake of fish and omega 3 fatty acids from seafood and the risk of cardiovascular disease in a prospective cohort study of 21,185 US male physicians who are participants in the Physicians' Health Study. In 4 years of follow-up, there were 281 incident cases of total (fatal and nonfatal) myocardial infarction, 173 cases of stroke, and 121 cardiovascular deaths. There was no evidence for association between dietary intake of fish and any cardiovascular endpoint, including myocardial infarction, stroke, and cardiovascular death. The relative risks of total myocardial infarction, adjusted for age and randomized treatment assignment, for categories of fish intake were: 1.0 for < 1 meal/week (referent), 1.6 (95% confidence interval (Cl) 1.1-2.3) for 1 fish meal/week; 1.4 (95% Cl 1.0-2.0) for 2-4 fish meals/week; and 1.2 (95% Cl 0.6-2.2) for > or = 5 fish meals/week; chi 2 for trend = 0.9, p = 0.34. The relative risks were similar for omega 3 fatty acid intake and for specific types of fish, and did not change after adjustment for history of hypertension, hypercholesterolemia, diabetes mellitus, or angina pectoris, parental history of myocardial infarction before age 60 years, obesity, exercise, smoking, alcohol use, saturated fat intake, and vitamin supplement use. These data do not support the hypothesis that moderate fish consumption lowers the risk of cardiovascular disease.