To test the hypothesis that the unusually low prevalences of insulin resistance (IR), metabolic syndrome (MS) and diabetes (DM) in Alaskan Eskimos, compared to American Indians, is related to the traditional Eskimo diet, high in C20-C22 omega-3 fatty acids (FAs). To determine if the relatively low blood pressures, low serum triglycerides and high HDL cholesterol levels in Eskimos result from high omega-3 FA consumption. Cross-sectional study. We measured plasma FA concentrations in 447 Norton Sound Eskimos (35-74 years of age) and screened for DM, CHD and associated risk factors. A dietary assessment (24-hr recall) was obtained for comparison the day before the blood sampling. Plasma omega-3 FA concentrations were highly correlated with dietary omega-3 FAs and HDL levels and inversely correlated with plasma levels of insulin, 2-h insulin (OGTT), HOMI-IR, 2-h glucose (OGTT), triglyceride levels and diastolic blood pressure. High consumption of omega-3 FAs positively affects components of the MS, insulin sensitivity and glucose tolerance. This finding suggests that high consumption of C20-C22 omega-3 FAs protects against the development of the MS and glucose intolerance.