Dietary intake of fish oils, rich in the polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has given inconsistent results as to their influence on the plasma fibrinogen level (1, 2, 3, 4, 5, 6). In the present study we have examined the effects of various fatty acids, the PUFAs and the saturated fatty acid palmitic acid (PA), alone or combined with the antioxidant vitamin E (Vit.E), on the fibrinogen concentration in the growth medium of human hepatoma (HepG2) cells. Vit.E alone decreased the amount of fibrinogen in the medium in a dose dependent fashion, where fibrinogen was measured as Fibrinopeptide A (FPA) releasable by thrombin. EPA and Vit.E decreased the amount of fibrinogen additively. PUFAs alone increased the fibrinogen concentration in a dose dependent manner. PUFAs combined with a fixed dose of Vit.E decreased the fibrinogen concentration, also dose dependently. OA and PA had an inhibitory effect, both alone and combined with Vit.E. These results indicate that Vit.E may be necessary for PUFAs to have a fibrinogen lowering effect, whereas both OA and PA apparently may decrease the fibrinogen concentration in the cell medium of HepG2 cells, both alone and combined with Vit.E. Possibly, peroxidation of the PUFAs may increase the fibrinogen production, that may be counteracted and reversed by the simultaneous presence of Vit.E.