Experimental diabetes in rats produces a generalized defect in liver microsomal polydesaturase activity and hence in the total fatty-acid composition. The present study was devised to determine whether or not those enzymic defects in the diabetic animal might be offset by alterations in the profile of fatty acids consumed in the diet. Accordingly, streprozotocin-induced diabetic rats were fed nutritionally adequate basal diets for 2 weeks supplemented with equivalent amounts of free fatty acids from either corn oil, rich in n-6 species, or cod-liver oil, abundant in n-3 acids. Both classes of dietary polyunsaturates were incorporated into hepatic microsomes and caused elevations in the respective levels of those acids in cellular membranes. The unsaturation indices, however, were higher under the latter regime than under the former. Dietary supplementation with the n-3, but not the n-6, fatty acids increased plasma glucose levels in both control and diabetic rats. Neither regime, however, affected microsomal desaturase or fatty acyl-CoA synthetase activity in either experimental group. Therefore, we conclude that the deficiency in hepatic-desaturase activity accompanying diabetes occurs independently of the nature of the fatty acids present in the hepatic membranes. An enhanced dietary intake of n-3 fatty acids thus fails to alleviate the depression in the enzymes involved in hepatic polyunsaturated fatty acid biosynthesis in diabetic rats.