Fish intake has long been recognized to play an important role in human health, for example, in reduction of the incidence of heart disease and some cancers and as immunosuppressors. In this study, we examined the effect of dietary supplementation with fish oils (FO) on monocytic procoagulant activity (PCA) in dogs. Six mongrel dogs were fed daily chow containing FO concentrate (MaxEPA, 0.5 g/kg body wt/day) for 8 weeks. Blood samples were drawn during a 20-week experimental period [i.e., before, during (weekly), and after (biweekly) MaxEPA supplementation] to measure monocytic PCA, PCA activation induced by endotoxin [lipopolysaccharide (LPS)], and plasma levels of total cholesterol, triglyceride, and fibrinogen (FBG). PCA was generally stimulated drastically by approximately 19-fold on incubation of whole blood with LPS (1 microg/ml) in vitro for 2 hr. The basal PCA remained essentially unchanged over the entire experimental period irrespective of MaxEPA supplementation; however, LPS-induced PCA activation was reduced by 50% (P < 0.05) 3 weeks after MaxEPA was introduced. This inhibition remained significant up to Week 10 and reached 75% at Week 12. Thereafter, PCA activation gradually returned to the level before supplementation. The plasma levels of total cholesterol, triglyceride, and fibrinogen were determined to be 178.8 +/- 6.0, 46.7 +/- 3.9, and 61.3 +/- 5.5 mg/dl, respectively. These plasma contents were neither correlated with LPS-induced PCA activation nor affected significantly by MaxEPA supplementation. Following a similar protocol, we also showed that MaxEPA supplementation resulted in a profound depression (-80%) of LPS-induced PCA activation in a rabbit, and PCA activation was eventually restored after removal of MaxEPA from the diet. Our results suggest a beneficial potential of MaxEPA supplementation in the management of atherothrombotic diseases in response to LPS infection.