The hypothesis is advanced that a gluconeogenic organ such as the liver would evolve to oxidise fatty acids as its source of ATP for gluconeogenesis. It is also argued that such an organ might, in the light of current knowledge, be expected to be ketogenic. The animals investigated were lamprey, rainbow trout, eel, toad, axolotl, lizard and rat. 2. The respiratory quotients of liver slices from all animals was close to 0.74. Ketone bodies were produced from butyrate by all livers excepting the lamprey and ketone bodies were present in all blood samples examined. 3. There was no convincing evidence that direct deacylation of acetoacetyl CoA was important in any liver. HMGCoA synthase activity could not be found in the livers of the lamprey and eel. This enzyme was present in livers of the other animals. There was a large amount of acetoacetyl CoA-succinate transferase in the livers of the rainbow trout and eel, but only small amounts in the higher animals. 4. It is suggested that, initially the transferase was the important ketogenic pathway and the HMGCoA pathway evolved later.
