Cultured astrocytes, transformed by Herpesvirus, were used as a model system to study several aspects of the control of glycogenolysis. Adrenergic agonists such as norepinephrine and isoproterenol caused an immediate and dose-dependent increase in the intracellular levels of cyclic AMP. Concomitant with the initial phase of cyclic AMP increase, conversion of phosphorylase b to a and glycogenolysis were observed. The elevation of cyclic AMP, phosphorylase conversion, and glycogenolysis were simultaneously blocked by beta-adrenergic blockers, but not by alpha-adrenergic blocking agents. Repeated administration of norepinephrine caused an attenuated response in both cyclic AMP accumulation and glycogenolysis. Glycogen degradation is also partially regulated by glucose availability. In the presence of glucose, norepinephrine-induced glycogenolysis is blocked, despite elevations in cyclic AMP. The direct role of glucose is postulated, since glucose analogs mimic the effects of glucose.