The concentration of insulin and glucagon in peripheral blood and the concentration of cAMP in liver was followed in rats throughout a 48 hour starvation period and up to 6 hours after refeeding glucose or casein. By so changing the insulin/glucagon molar ratio from minimum to maximum values, simultaneous inverse changes in the concentration of hepatic cAMP could be induced. The study, thus, suggests that during a starvation-refeeding cycle the level of cAMP in the liver is regulated predominantly by the insulin/glucagon ratio in the blood. Possible criticisms of this conclusion are discussed.