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Eicosapentaenoic acid (EPA), a polyunsaturated fatty acid analog of arachidonic acid, alters certain platelet functions controlled by prostaglandins and thromboxanes, probably by inhibiting the synthesis of these molecules from arachidonic acid. This study reports the effects of a diet enriched in EPA (fish-fat diet, FFD) as compared with a diet lacking EPA (beef-fat diet, BFD) upon certain immunological and inflammatory responses in outbred Sprague Dawley rats. Induction of antibody formation to egg albumin (EA) produced four- to eight-fold greater titres of IgE (P < 0.02) and IgG (P < 0.03) anti-EA antibodies in FFD rats v. BFD rats. FFD rats had heightened active cutaneous anaphylaxis to EA, responding to a median [EA] of 10-4 mg/ml, v. 10-3 mg/ml in BFD rats (P<0.0032). Similarly, active Arthus reaction to EA in FFD rats was elicited to a [EA] of 10-3 g/ml v. 10-1 g/ml in BFD rats (P < 0.01). Passive inflammatory reactions, as evaluated by passive cutaneous anaphylaxis elicited with IgE antibody, and by the intradermal injection of aggregated IgG, were not significantly different between the two groups. EPA constituted 7.3% of fatty acid in the livers of FFD rats, v. 0.3% in BFD rats (P<0.01). These data demonstrate enhanced levels of IgE and IgG antibody in FFD rats, with subsequent increased active inflammatory reactivity in these animals. These alterations may be secondary to enrichment of tissue lipids with EPA, although effects due to changes in other fatty acids have not been excluded. [ABSTRACT FROM AUTHOR]