We examined the effect of a fish oil-enriched diet on the development of experimental membranous nephropathy in the rat induced by administration of cationic bovine gamma globulin (CBGG). Rats were placed on a fish oil-enriched diet and control rats received a diet containing an equivalent amount of beef tallow. After 6 weeks on either diet, rats were pre-immunized and injected with CBGG. Proteinuria was significantly reduced in the fish oil-fed group as compared to the control group (160 +/- 40 mg/24 hours, n = 15, versus 280 +/- 36 mg/24 hours, n = 17, p less than 0.02). Glomerular filtration rate was also significantly higher in the fish oil-fed rats than in controls (0.91 +/- 0.07 ml/minute, n = 11, versus 0.60 +/- 0.05 ml/minute, n = 10, p less than 0.005). Glomerular production of prostaglandin E2 and thromboxane B2 the stable product of thromboxane A2, were inhibited by 68% and 70%, respectively, by the fish oil-enriched diet (n = 8, p less than 0.01 versus control). Glomerular leukotriene B4 was also inhibited by 50% in the fish oil-treated rats (n = 6, p less than 0.01), but inhibition of leukotriene B4 by the specific inhibitor L-663,536 in control rats did not ameliorate proteinuria. There was no difference in the amount of distribution of glomerular immune deposits as demonstrated by immunofluorescence and electron microscopy between the experimental and control groups. Moreover, comparable amounts of glomerular IgG deposits were present in the two groups. The specific immune response, assessed by measuring anti-BGG antibody levels, was not different between the two dietary groups, while more than 85% suppression of the splenic T- and B-cell mitogenic response to concanavalin-A and lipopolysaccharide was noted in rats fed the fish oil-enriched diet. We conclude that a fish oil-enriched diet reduces proteinuria and preserves the glomerular filtration rate in rats with CBGG-induced membranous nephropathy. Its mechanism of action remains to be established.