To test whether the property of medium-chain fatty acids (which have 6-12 carbon atoms) being incorporated only in small amounts into the various tissues of a living organism could be exploited to treat obesity, genetically obese Zucker rats and their lean littermates were fed a diet containing 20% medium-chain triacylglycerols (MCT) or long-chain triacylglycerols (LCT) for 10 weeks. MCT, as compared with LCT, had the following effects: 1) MCT did not diminish weight gain in either the nonobese or the obese rats; 2) they increased ketogenesis more in the former than in the latter; 3) they increased the concentration of triacylglycerols in the liver of the obese rats but not of the lean ones; 4) they decreased the concentration of cholesterol in the liver of the lean but not of the obese rats, and 5) they did not particularly affect the concentration of proteins, glucose and insulin in the blood. We therefore conclude that the influence of the genotype is much more important in the establishment of the biochemical characteristics of rats than is the nature of the fatty acids ingested. Replacing LCT in the diet with MCT did not correct any of the major metabolic disorders in obese rats and therefore cannot unaided constitute a solution to the problem of genetic obesity.