The effect of a diet enriched in fish-oil-derived fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DCHA) in inflammation and immunological processes in rats has been investigated. Rats on a normal chow diet were given 500 mg/kg/day EPA and 333 mg/kg/day DCHA by gavage over a period of 50 days. Control groups received water, oleic acid or safflower oil. Acute and chronic phases of inflammation induced by antigenic challenge with bovine serum albumin were examined in the rat air-pouch model. In rats receiving fish-oil-derived fatty acids, there was a reduced production of the arachidonic acid metabolites, prostaglandin E2 and leukotriene B4, in the exudate in the chronic phase of inflammation, but not in the acute phase. This was associated with an increased infiltration of leukocytes, especially monocytes and macrophages, in the chronic inflammatory phase. The fish-oil-supplemented diet showed no effect on the volume of inflammatory exudate, the amount of protein in the exudate and connective tissue proliferation. Carrageenin-induced paw edema in the animals was not influenced by the diet. There was no effect of the dietary fish oil on production of antibodies to bovine serum albumin in the rats. However, the diet appeared to suppress a delayed-type skin reaction in the animals. These studies suggest that fish-oil-derived fatty acids may modulate chronic inflammation and a cellular-mediated immunological reaction by reducing the synthesis of arachidonic acid metabolites.