1. 1. The effects of glucagon, epinephrine and insulin on the in vivo time course changes in blood glucose and in blood, muscle and liver cyclic AMP levels of the domestic fowl have been studied. 2. 2. Intravenous injections of glucagon and epinephrine produced a rapid increase in blood cyclic AMP (10- and 6-fold, respectively) followed by a more gradual increase in blood glucose. The patterns of response, however, in blood, muscle and liver, following either glucagon or epinephrine administration were different. Glucagon markedly elevated hepatic tissue levels while it had only a minimal effect on muscle. Epinephrine, in contrast, elevated cyclic AMP levels to a similar extent in both tissues. The decrease in peak cyclic AMP levels following epinephrine treatment was biphasic for both muscle and liver. 3. 3. The time course patterns for the rise and fall of cyclic AMP in liver, muscle and blood were nearly the same suggesting a rapid transfer of tissue cyclic AMP to blood. Maximal cyclic AMP levels occurred 5–10 min and 10–20 min after intravenous injections of epinephrine and glucagon, respectively. 4. 4. Insulin depressed blood glucose levels but elevated blood, muscle and liver cyclic AMP levels. The cyclic AMP pattern following insulin injection is different than that observed in mammals.