2 The free internal Ca+ concentration in human red cells is set according to the leak 2 and-pump principle: There is a finite passive Ca+ influx at the physiological 2 2 Ca+ -gradient across the membrane which is compensated by Ca+ pumping in the outward direction with a rate given by the degree of saturation of the A TP-fuelled Ca 2 pump at the steady-state internal Ca+ concentration. Simons (1982) recently devised a method allowing the measurement of the steady 2 2 state internal Ca+ concentration. Cells are suspended in media of different Ca+ con 2 2 tent whose Ca+ concentration is monitored by a Ca+ -selective electrode. When the cells are lysed (by digitonin) there is an upward or downward deflection of the elec 2 trode signal. At the point of zero deflection, the cellular Ca+ concentration equals that 2 of the medium. The result is, that in fresh human red blood cells the Ca+ concentra tion is ;;;; O.4,uM (this is an upper estimate; the true value may be considerably lower).