The effects of long-term feeding of 2 or 10% fat diets containing corn oil, beef tallow, or menhaden oil on the levels of eicosanoids in brain, plasma, and kidney medulla were studied. Male BHE/cdb rats, which carry a genetic trait for non-insulin-dependent diabetes mellitus, were fed these diets for 9 mo, at which time their glucose tolerance levels were determined, as were brain, kidney medulla, and plasma levels of PGE2, 6-keto-PGF1 alpha, and LTB4. Glucose tolerance was abnormal in the 2 and 10% corn oil groups and normal in the 10% menhaden oil groups. The glucose tolerance levels of the other groups were only slightly disturbed. The levels of LTB4 in kidney and plasma were not affected by dietary fat type or amount. LTB4 levels were significantly higher in the brains of rats fed a low level of beef tallow than in the brains of rats fed a higher level of beef tallow or a low level of menhaden or corn oil. LTB4 values for the brains of rats fed the other diets were intermediate and not different from the aforementioned values. The levels of 6-keto-PGF1 alpha were highest in rats fed the 10% corn oil diet regardless of the tissue assayed. Rats fed the 2 or 10% beef tallow or menhaden oil were not different but had lower levels of this eicosanoid metabolite than rats fed the corn oil diet. PGE2 levels followed the same pattern, suggesting that the impaired glucose tolerance of the corn oil-fed rats had a strong influence on the tissue levels of these eicosanoids.