Rh-pos. human red cells sensitized with IgG-Anti-D showed at 4 degrees C an intracellular Na+-accumulation, which was amplified by an increase in the Na+-concentration in the incubation medium. This increase of the intracellular Na+-concentration may be due to a passive Na+-influx since the Na+-K+-ATPase system does not work at this temperature. At the optimal reaction-temperature of the enzyme the Na+-K+-ATPase activity of the sensitized Rh-pos. red cells was inhibited proportionally to the anti-D concentration. Both the amplified Na+-influx and the inhibition of the active Na+-transport caused an osmotic hemolysis. The hemoglobin release was significant above the anti-D titer step of 1:512. This mechanism suggests that the intravasular part of the immunohemolysis with Rh incompatibility was generated by an impaired active and passive cation transport following the antigen-antibody reaction. This suggestion is supported by the fact that IgG-Anti-D neither stimulated the complement system nor the intravascular monocyte mediated cell lysis, since the activity of the effector cells is reduced by the surplus of sensitized red cells and the presence of other inhibiting IgG immunoglobulins. The biochemical relationship of the Rh-D-antigen and the Na+-K+ATPase both located on membrane lipoproteins, may be the reason why only the antigen-antibody reaction in the Rh-D system impaired the cation transport. The antigen-antibody reaction of IgM-Anti-A and of the cold agglutinin IgM-Anti-I reacting with glycolipid and with glycoprotein membrane antigens respectively did not impair the cation transport after complement inactivation.