The effect of internal and external pH, on the components of the Ca2+ efflux have been investigated in internally displayed squid axons. (1) Internal pH: a fall in intracellular pH (below 7.3) inhibited both the ATP-dependent uncoupled (Ca2+ pump) (50% at pHi 6.3) and the Na+o-dependent Ca2+ efflux (forward Na+/Ca2+ exchange) (50% at pHi 6.8). Internal alkalinization of pH 8.8 had no effect on the uncoupled component but markedly increased (4-fold) the Na+o-dependent Ca2+ efflux. (2) External pH: altering the external pH from 7.3 to 9.0 had no effect on the Na+o-dependent Ca2+ efflux mechanism. In the absence of Ca2+o, alkalinization to pHo 8.8 caused a reduction in the magnitude of the uncoupled Ca2+ pump. This inhibition is markedly enhanced by the presence of Ca2+ in the external medium. As for the case of the sarcoplasmic reticulum Ca2+-ATPase, this combined inhibitory effect of high pHo and Ca2+o is most probably related to a reversal of the cycle of the ATP driven Ca2+ pump. The marked differences in the pH dependence of the components of the Ca2+ efflux support the model of two separate mechanisms of Ca2+ extrusion in squid axons: Ca2+ pump and Na+/Ca2+ exchange.