Effects of dietary carbohydrates on triglyceride production and hepatic lipogenic enzyme activities were examined in Wistar fatty rats, an animal model of noninsulin dependent diabetes mellitus, fed fructose or glucose and were compared with those of Wistar lean rats. Carbohydrates were supplied in 10% drinking solutions for 21 days. As compared with lean rats, Wistar fatty rats were characterized by hyperglycemia, hyperinsulinemia and hypertriglyceridemia, the last of which was associated with an increased hepatic activity of fatty acid synthetase and an increased rate of triglyceride secretion from the liver to the circulation. Feeding fructose to genetically obese diabetic rats produced a threefold increase in the hepatic activity of fatty acid synthetase, a twofold increase in NADPH-generating enzymes (malic enzyme and glucose-6-phosphate dehydrogenase) and a 56% increase in the rate of triglyceride secretion, with a resultant 86% increase in plasma triglyceride concentrations. Feeding glucose produced a similar increase in the activity of NADPH-generating enzymes and triglyceride production in the fatty liver but it differed in producing no change in plasma triglyceride concentrations or hepatic fatty acid synthetase activity. Neither dietary fructose nor glucose changed glycemia or insulinemia. These results show that in genetically obese, diabetic rats feeding fructose and glucose is associated with an increase in hepatic lipogenic enzyme activities and triglyceride production, and suggest that fructose stimulates triglyceride production but impairs triglyceride removal, whereas glucose stimulates both of them.