1. Rapid effects of hormones on the metabolism of glycogen and fatty acids were studied in the perfused liver of normal and genetically obese (ob/ob) mice.
2. In livers from normal and obese mice adrenaline and angiotensin II stimulated glycogenolysis.
3. These hormones inhibited the synthesis de novo of long-chain fatty acids in livers from normal mice, but not in livers from obese mice.
4. The proportion of acetyl-CoA carboxylase in the active form was decreased by adrenaline but not by angiotensin II in livers from obese mice.
5. The potency of hormone effects on liver suggests that they could occur in the intact animal.
6. The results add to the evidence that hepatic fatty acid synthesis in genetically obese (ob/ob) mice is irreversibly resistant to inhibition by a range of hormones. Such resistance could be of primary significance in the pathogenesis of the obesity.