To compare their relative absorption and effect on platelet function, concentrated fish oil and tuna were given to 10 subjects in a randomized crossover study. Although plasma enrichment of eicosapentaenoic acid (EPA) from either preparation was similar, relative absorption of EPA from tuna was significantly greater than that from fish oil (46.6 +/- 3.0 mg.L-1.g EPA-1 from tuna compared with 16 +/- 1.0 mg.L-1.g EPA-1 from fish oil, P less than 0.001). Relative absorption of docosahexaenoic acid (DHA) was equivalent (54.0 +/- 9.0 mg.L-1.g DHA-1 from tuna, 56 +/- 9.0 mg.L-1.g DHA-1 from fish oil, NS). Platelet aggregation in response to the endoperoxide analog U46619 was significantly diminished after either preparation but aggregation in response to other agonists, bleeding time, and membrane n-3 (omega-3) fatty acid content were not changed. Thus, n-3 fatty acids are well absorbed after one dose of either tuna or fish oil but EPA absorption appears to be more efficient from tuna. Additionally, a single dose of n-3 fatty acids decreases platelet aggregation by a mechanism not requiring incorporation into platelet membranes.