The intracellular ionized calcium concentration ([Ca2+]i) in squid axons is far below that expected at equilibrium, and Ca2+ must therefore be extruded against a large electrochemical gradient in order to maintain the steady state. In the absence of ATP, Ca efflux from internally-dialyzed axons is largely dependent on external Na, and is associated with a Cai-dependent Na influx. An Nai-dependent Ca influx and Cao-dependent Na efflux have also been observed in squid axons. The data imply that the axolemma has a "carrier" mechanism that can mediate the counterflow exchange of Na+ for Ca2+. Several observations indicate that the stoichiometry of the exchange is about 3 Na+-for-1 Ca2+:a) Ca efflux appears to be a cubic function of external Na concentration; b) Ca efflux is reduced when the membrane is depolarized; and c) the Nao-dependent Ca efflux is about 1.5 pmoles/cm2-sec when free [Ca2+]i is about 160 mum, while the Cai-dependent Na influx is about 5 pmoles/cm2sec. If the stoichiometry is 3-for-1, the Na electrochemical gradient, alone, could provide sufficient energy to maintain [Ca2+]i at about 50-200 nM. ATP also influences the Ca efflux: it appears to increase the affinity of the transport mechanism for internal Ca, but does not affect the maximum velocity of transport. Thus ATP may catalyze, but not necessarily energize Ca transport.