The effect of intravenous epinephrine on heart glycogen synthase and phosphorylase systems in control and insulin pretreated rats was studied. The percent of synthase in the I form decreased rapidly after epinephrine treatment but the change was small and sometimes not significant. In insulin pretreated rats in which the percent synthase I was increased, epinephrine produced a definite and highly significant decrease. There was a simultaneous increase in percent phosphorylase a in both groups. The synthase and phosphorylase responses were statistically significant at 2.5 μg epinephrine/kg or more. These data are compatible with a mechanism in which protein kinase is activated by an increased cAMP concentration and affects both the synthase and phosphorylase systems simultaneously. Propranolol blocked the epinephrine effects on cAMP, synthase I, and phosphorylase a. Although insulin had little effect on the response of the synthase and phosphorylase systems to epinephrine, it nearly completely blocked glycogen degradation. The mechanism is unknown, but it appears to be due to an inhibition of phosphorylase a catalytic activity in vivo. Acetylcholine had no effect on synthase I, phosphorylase a, or cAMP in control or in insulin pretreated animals.