The effects of dietary fish oil, MaxEPA, and corn oil on insulin sensitivity were examined in male miniature pigs. The pigs (20-35 kg) received 750 g of nonpurified diet per day (160 g/kg protein, 50 g/kg fat) with the addition of either 30 g corn oil or 30 g MaxEPA, resulting in 90 g total fat per kg diet for 4-5 wk. The MaxEPA diet provided 12.6 g (n-3) polyunsaturated fatty acids per kg diet (6.7 g eicosapentaenoic acid, 4.8 g docosahexaenoic acid), 4.7 g (n-3) polyunsaturated fatty acids and 147 mg cholesterol. The corn oil diet provided 22.7 g (n-6) polyunsaturated fatty acids per kg diet and no (n-3) polyunsaturated fatty acids; cholesterol was added to equal the amount in the MaxEPA. After overnight withdrawal of food, intravenous glucose tolerance tests were conducted in conscious pigs by using previously placed jugular vein catheters. Plasma glucose responses and the areas under the plasma glucose curves were similar in seven MaxEPA- and five corn oil-fed pigs. However, the incremental areas under the insulin curves were significantly lower for the pigs fed MaxEPA. Thus values for insulin sensitivity (SI), determined with Bergman's minimal model, were significantly higher for MaxEPA than for corn oil-fed pigs, whereas the rate of glucose disappearance (KG), did not differ between the two groups. Therefore, substitution of (n-3) for (n-6) polyunsaturated fatty acids in dietary lipids is associated with enhanced insulin sensitivity in male pigs.