A dose-response study of dietary fish oil supplementation on platelet adhesion was performed in three groups of five normal individuals each. Fish oil equivalent to 3, 6, or 9 g eicosapentaenoic acid (£PA)/day was administered for 3 weeks, and platelet adhesion was evaluated under high and low shear rate conditions in a laminar flow chamber before, during, and after termination of fish oil administration. Platelet adhesion to collagen I and fibrinogen, the two test surfaces in this study, was greatly reduced in response to fish oil. The inhibitory effect was similar whether platelet adhesion was evaluated at high or low shear rates. Maximal inhibitory activity was noted at 6 g EPA/day. A delayed onset and prolonged washout period characterized the response. The washout period of the fish oil effect was inversely related to the level of dietary supplementation. Measurement of total fatty acid distribution in platelets showed a dose-related increase in n-3 polyunsaturated fatty acids. From these studies, it is concluded that fish oil is an effective inhibitor of platelet adhesion, which reaches its maximum effect at approximately 6 g EPA/day.