The frequency dependent accumulation of cations by erythrocytes in alternating currents (ac) involves the membrane Na,K-ATPase. We have suggested that frequency dependent ion concentration changes could account for the effect of ac on the ion-activated Na,K-ATPase. Support for this idea has come from studies of ATP splitting by the enzyme when ac (over a range of amplitudes and frequencies) flows through Na,K-ATPase suspensions via platinum electrodes/salt-impregnated agar gels. Ac signals decrease ATP splitting by the normal enzyme, with the maximum effect at 100 Hz, and increase the enzyme activity, when the activity is lowered in different ways, including introduction of ouabain. The quantitative dependence of the enzyme activity in the ouabain experiments suggests that ac antagonizes the inhibition in a way that is consistent with ion competition at a binding site. Inhibition and activation by ac as well as ion competition and frequency dependence can be explained by variations in ion activation. Such a mechanism could account for the effects of electromagnetic fields on biological systems, since the threshold field estimated by extrapolation of our measurements is 20 μV/cm, within the range of reported biological effects. © 1990, All rights reserved.