The mechanism of adrenergic swelling, cAMP accumulation and associated Na+ and K+ concentration changes was investigated in amphibian Rana ridibunda erythrocytes. The addition of noradrenaline to an isotonic suspension of red cells of frog Rana ridibunda in the presence of the phosphodiesterase inhibitor isobutyryl-methylxanthine (IBMX), induced a significant increase of the cell volume. Forskolin treatment showed analogous results. The removal of the Na+ from the incubation medium, inhibited the volume changes caused by either noradrenaline or forskolin. Under the same conditions a more than two-fold increase of lactate formation, 260% increase of glucose consumption and accumulation of cAMP were found. These effects are specific and rapid. The peak of lactate production at 7.5 min was followed by a slow further decrease, whereas cAMP reached a plateau after 15 min. The increased glycolytic rate is probably the consequence of an activation of phosphofructokinase by cAMP. When the red cells were incubated in the presence of either noradrenaline or the cAMP analog, dibutyryl-cAMP the intracellular concentration of Na+ was significantly increased by the first 7.5 min of incubation compared with the initial values. Both the adrenergic activation and dibutyryl-cAMP treatment induced an intracellular decrease in the K+ content by 15%. In the presence of amiloride the Na+ and the K+ content of erythrocytes remained unaltered. Cellular swelling may be a prerequisitive for activation of Na+ and K+ movements. These findings suggest a regulatory role of cAMP in the energy metabolism of Rana ridibunda erythrocytes. In addition, the adrenergic responses were rapid and specific to alpha 1 and beta-antagonists.