Recent epidemiological evidence indicates that the hemostatic profile is an important predictor of cardiovascular disease, yet its dietary determinants are not well established. An important question is whether dietary fatty acid intake influences blood levels of coagulation proteins. We examined potential dietary determinants of six hemostatic factors--fibrinogen, factor VII, factor (vWF), protein C, and antithrombin III--in four population-based samples totaling over 15,000 participants, blacks and whites, in the Atherosclerosis Risk in Communities (ARIC) Study. Usual dietary intake was assessed by a food frequency questionnaire. Cross-sectional associations were explored using multiple linear regression analysis, adjusting for gender, race, age, body mass index, smoking status, alcohol use, diabetes, and field center. Dietary intake of n-3 polyunsaturated fatty acids (PUFAs) showed negative associations with fibrinogen, factor VIII, and vWF (blacks and whites) and a positive association with protein C (whites only). Fish intake, the major source of dietary n-3 PUFAs, was similarly related to the hemostatic profile: a 1 serving per day greater fish intake was associated with the following predicted differences (95% confidence interval): fibrinogen, -2.9 mg/dL (-6.3, 0.5); factor VIII, -3.3% (-5.4, -1.3); vWF, -2.7% (-5.2, -0.1) (blacks and whites); and protein C, +0.07 microgram/mL (0.03, 0.11) (whites only). Other nutrients or foods were variably associated with the hemostatic factors. These population-based associations, although cross-sectional, suggest that increases in n-3 PUFA intake from fish may modify the blood levels of several coagulation factors.