In the presence of ATP and of Mg 2+ , human erythrocyte membranes show a phosphatase activity towards p -nitrophenyl phosphate which is activated by low concentrations of Ca 2+ . The effect of Ca 2+ is strongly enhanced if either K + or Na + is also present. Activation of the p -nitrophenyl phosphate phosphatase by Ca 2+ reaches a half-maximum at about 8μ m -Ca 2+ and is apparent only when the ion has access to the inner surface of the cell membrane. Ca 2+ -dependent phosphatase activity can only be observed if ATP is at the inner surface of the cell membrane, and the presence of ATP seems to be absolutely necessary, since either its removal or its replacement by other nucleoside triphosphates abolishes the activating effect of Ca 2+ . The properties of the (ATP+Ca 2+ )-dependent phosphatase are very similar to those of the Ca 2+ -dependent ATPase (adenosine triphosphatase), also present in erythrocyte membranes, which probably is involved in Ca 2+ transport in erythrocytes. The similarities suggest that both activities may be properties of the same molecular system. This view is further supported by the fact that p -nitrophenyl phosphate inhibits to a similar extent Ca 2+ -dependent ATPase activity and ATP-dependent Ca 2+ extrusion from erythrocytes.