The capacity of erythrocytes to modify their glycogen stores to compensate for changes in glucose concentration in plasma was studied. Experiments in vitro and in vivo demonstrated that erythrocytes absorbed and incorporated glucose into their glycogen stores when glucose concentration in the medium was high and liberated it when the concentration was low. Epinephrine administration inhibited glucose absorption by erythrocytes, and in its presence, erythrocytes liberated glucose from their glycogen stores, being unable to compensate for this rise in glucose concentration in plasma. Similar results were obtained when endogenous secretion of epinephrine was enhanced by carotid sinus-chemoreceptor stimulation. Insulin had no effect on the capacity of erythrocytes to absorb glucose. These data suggest a role for erythrocytes in the transport of glucose to different regions in the organism's circulation and in the regulation of glucose concentration in plasma.