Abstract Salts of the ketone acids, Na-beta-hydroxybutyric acid and Na acetoacetic acid, were injected intravenously into the normal rat and produced a sharp decrease in plasma FFA levels which persisted for one hour. No significant changes in levels of plasma glucose or insulin were observed. In vitro studies were performed using epididymal fat pads. Ketone acids were added to make a final concentration of 10 mmoles each. There was no significant effect on tissue glycogen, incorporation of labeled glucose into glycogen or production of C 14O 2, but there was an increase in the incorporation of C 14 into tissue lipids. The release of FFA and glycerol into medium was decreased. In another group of experiments, ketone acids were injected subcutaneously twice a day for three days. Adipose tissue from these animals reacted with increased glycogen, C 14-glycogen, C 14O 2 and C 14-lipids, and decreased release of FFA and glycerol. The impaired reaction of the adipose tissue of alloxan diabetic rats improved after treatment of these animals with ketone acids for three days. From these studies, we conclude that ketone acids have a minimal direct action on glucose metabolism in adipose tissue but a marked effect on fat metabolism with a definite decrease in FFA and glycerol release. Adipose tissue from ketone-acid-treated animals showed an insulin-like response suggesting that these acids in vivo do stimulate the insulin secreting cells of the pancreas. Both effect on fat tissue, direct and by employing insulin, result finally in a decrease of blood FFA levels; this may be of importance in prevention of development of severe ketoacidosis.