The present account contains a brief summary of the concept of the glucose fatty acid cycle and of the experimental evidence on which it is based and of its possible importance in the interpretation of metabolic disturbances in obesity and maturity onset diabetes. Much of the experimental evidence on which the concept is based has been published in detail elsewhere.''The concept of the glucose fatty acid cycle is concerned with a reciprocal relationship between the metabolism of glucose and of fatty acids in muscle and adipose tissue. It is based upon the inhibitory effects of glucose and insulin on the release of fatty acids from glycerides in the two tissues and upon the inhibitory effects of fatty acid oxidation on the metabolism of glucose by glycolysis and oxidation in muscle and the action of insulin thereon. Adipose tissue may contribute to the oxidation of fatty acids in muscle because of its role as a source of plasma non-esterified fatty acids (NEFA). In normal animals the functioning of the cycle leads to the release and oxidation of fatty acids and to suppression of glucose oxidation during periods of carbohydrate deprivation. After intake of carbohydrate the release and oxidation of fatty acids is promptly suppressed and the uptake and oxidation of glucose is facilitated. The release of insulin from pancreatic 0 cells which is stimulated by glucose is an important factor in these changes. In alloxan-diabetes in the rat the cycle is disturbed in such a way that fatty acids continue to be oxidised in muscle at an accelerated rate for some time after the provision of glucose and insulin. This accelerated rate of fatty acid oxidation leads to impaired uptake, glycolysis and oxidation of glucose in the presence of insulin and it appears to be an important factor in the insulin insensitivity or antagonism exhibited by muscles of diabetic rats. The most direct evidence for the glucose fatty acid cycle and for the view that many disturbances of glucose metabolism in muscle in diabetes are secondary manifestations of accelerated release and oxidation of fatty acids have been obtained in in vitrv experiments with rat muscle. These are summarised in the following section. Possible extensions of the cycle to liver where increased rates of fatty acid oxidation may accelerate gluconeogenesis are also briefly considered. In maturity onset diabetes and in established obesity there is evidence that the cycle is disturbed in such a way that fatty acids may be released and oxidised at an accelerated rate in spite of the presence of adequate amounts of circulating glucose and insulin. This has raised the possi-