Studies were conducted to clarify the effects of vasopressin, angiotensin II and phenylephrine on hepatic ketogenesis and fatty acid synthesis. Hepatocytes from fed rats were incubated with oleate or octanoate. Vasopressin stimulated fatty acid synthesis as well as lactate and pyruvate accumulation in the presence of oleate. In accordance with this action, vasopressin caused a marked decrease in ketogenesis from oleate. When octanoate was added as a substrate, vasopressin failed to inhibit ketogenesis. Neither angiotensin II nor phenylephrine affected ketogenesis or fatty acid synthesis. The results in the present study show that there are vasopressin-mediated reciprocal changes in ketogenesis from oleate and fatty acid synthesis in isolated hepatocytes.