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 definate and highly significant decrease. There was a simultaneous increase in percent phosphorylase a in both groups. The synthase and phosphorylase responses were statiscally significant at 2.5 mug epinephrine/kgor 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 phosphorylasesystems simultaneously. Propranolol blocked the epinephrine effects on cAMP, synthase I, and phosphorylase a. Although insulin had little effect on the response ofthe synthase and phosphorylase systems to epinephrine, it nealry 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.