The effects of beta-adrenergic stimulation of adenylate cyclase on energy metabolism of rat reticulocytes were studied. A large initial rate of cAMP formation induced a rapid short-term stimulation of glycolysis which was followed by an exponential decline at maintained high cellular cAMP level. The decrease of glycolytic activity signifies a "metabolic desensitization" by a permanently increased cAMP concentration. Stimulation of PFK activity was found to be the main reason for the increased glycolytic rate which is due to the several fold increase of cAMP and in part to ATP-depletion. Total and coupled respiration, as well as the ATP/ADP ratio were not changed. The data indicate that stimulation of adenylate cyclase of reticulocytes selectively activates glycolysis, i.e. the cytosolic energy compartment with no detectable influence on oxydative phosphorylation.