Modifications in membrane fatty acid composition and insulin action are possible through dietary intervention. We examined the metabolic fate of (n-3) fatty acids in male Wistar rats, using three isocaloric, high fat diets. The ET-L, OL-L and SAF-L diets contained edible tallow, olive oil and safflower oil, respectively, with identical amounts of (n-3) fatty acids as linseed oil. Despite isocaloric feeding, weight gain was lower (P < 0.001) in rats fed the more highly saturated ET-L diet (69 +/- 8 g) than in those fed either the high (n-9) fatty acid OL-L diet (93 +/- 2 g) or the high (n-6) fatty acid SAF-L diet (108 +/- 4 g). Analysis of red quadricep fatty acid composition revealed phospholipid (n-3) fatty acid levels in the ET-L-fed group (21.6 +/- 0.8 g/100 g fatty acids) to be significantly higher than in either the OL-L-fed (17.7 +/- 0.6 g/100 g fatty acids, P < 0.05) or SAF-L-fed (15.3 +/- 0.7 g/100 g fatty acids, P < 0.05) group. A similar pattern was observed in other muscles and white adipose tissue. A follow-up study using 14C-labeled (n-3) fatty acids in the diet showed greater (n-3) fatty acid incorporation in the ET-L-fed group relative to the other two groups and conversely lower 14CO2 production than in the SAF-L-fed group. These results demonstrate that metabolic fate of dietary fatty acids is strongly influenced by the overall fatty acid profile of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)