The influence of a moderate dietary supplementation with omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (3.4 g eicosapentaenoic and docosahexaenoic acids per day) for six months on lipopolysaccharide (LPS) stimulated monocyte procoagulant activity (PCA) was studied in two series of experiments, evaluating the plasma and cellular phases, respectively. In the first series, standard cryopreserved monocyte cultures were examined in heparin plasma of atherosclerotic patients (n = 24, 12 given omega-3 PUFAs, 12 controls). In the second series, monocytes from patients (n = 32, 16 given omega-3 PUFAs, 16 controls) were investigated in a standard plasma milieu. Plasma and monocytes were obtained from the test subjects before as well as after six months of omega-3 PUFA supplementation. Monocyte PCA, measured by the formation of fibrinopeptide A, was not significantly different when comparing plasma and monocytes from the subjects supplemented with omega-3 PUFAs with plasma and monocytes, respectively, from the control subjects. In the second series of experiments we also determined the LPS induced release of interleukin-6 (IL-6), which was not significantly different in the two groups. However, a strong correlation between the stimulated monocyte IL-6 release and PCA was demonstrated (r = 0.70, p = 0.00001), probably reflecting an individual inflammatory response pattern.