The study was designed to determine whether overfeeding rats with a diet containing medium-chain triglyceride (MCT) as the major fat source (45% of calories) would impede the expected gain in weight and body fat as compared to rats overfed with isocaloric amounts of diet containing long-chain triglyceride (LCT). For 6 wk rats were fed either MCT diet or LCT diet twice daily via a gastrostomy tube. MCT-fed rats gained 20% less weight (P less than 0.001) and possessed fat depots weighing 23% less (p less than 0.001) than LCT)-fed rats. Mean adipocyte size was smaller (p less than 0.005) in MCT- than in LCT-fed rats. Weights of carcass protein and water were similar for both groups as were concentrations of serum insulin and levels of physical activity. The decreased deposition of fat in the MCT-fed rats may have resulted from obligatory oxidation of MCT-derived fatty acids in the liver after being transported there via the portal vein, leaving almost no MCT derivatives for incorporation into body fat. MCT may have potential for dietary prevention of human obesity.