Major risk factors for coronary heart disease were assessed in two populations of Tanzania, one on a fish diet (FD) living along the coast of Lake Nyasa, and the other, mainly on a vegetarian diet (VD), living in a farming area. Lower blood pressure values were found in the FD subjects (n = 618) vs. VD (n = 618) (systolic blood pressure, SBP, 120 +/- 15 vs. 135 +/- 20, P < 0.01; diastolic blood pressure, DBP, 70 +/- 9 vs. 78 +/- 11, P < 0.01, respectively). In an FD subgroup (n = 61), total cholesterol (TC) (122 vs. 136 mg/dL, P < 0.01); triglycerides (TG) (82 vs. 105 mg/dL, P < 0.01); and lipoprotein (a) [Lp(a)] (19.9 +/- 18.4 vs. 32.3 +/- 22.4, P < 0.001) were lower than in a VD subgroup (n = 55). Serum fatty acids (FA) in the FD subgroup were as follows: eicosapentaenoic acid (EPA) (20:5) 2.48 vs. 0.72%, docosahexaenoic acid (DHA) (22:6) 5.93 vs. 1.49%, vs. the VD, respectively. Arachidonic acid (AA) (20:4n-6) also was higher in the FD vs. the VD group (9.85 vs. 8.30%, P < 0.05), whereas 18:2n-6 was about double (23.97 and 14.85%) in VD vs. FD. The peculiar serum FA pattern in FD reflected the FA of dietary fish. In fact, in four main species of lake fish, DHA was 8-19%, higher than EPA (1.8-4.2%), in contrast with the situation in cold-water fish, and AA was 5.8-8%, higher than in cold-water fish. The data, obtained in populations strictly on natural, unprocessed, low-fat diets, show that a diet based on freshwater fish results in lower BP, serum TC, TG, and Lp(a), and suggests that serum AA is not reduced when the major dietary n-3 is DNA rather than EPA.