Diabetes is associated with hypertriglyceridemia and it has been suggested that the intestine contributes to this elevation. Recent studies have shown that in animals with IDDM, fatty acid (FA) synthesis is decreased in the liver and increased in the small intestine (SI). The purpose of the present study was to measure FA synthesis in the liver and SI of animals with NIDDM. In both db/db and ob/ob animals the incorporation of 3H2O into FA was increased in the SI (10 fold in db/db and 2.2 fold in ob/ob). FA synthesis was also increased in the liver of NIDDM (9 fold in db/db and 6 fold in ob/ob). These results provide further evidence that diabetes leads to changes in lipid metabolism in the SI.