Inactivation of the Ca channel of Aplysia neurons was studied in the absence of potassium current in cells that were cesium-loaded with the aid of the ionophore nystatin. Inactivation was substantially decreased by methods that limited Ca entry. Depolarizations commensurate with the equilibrium potential of Ca resulted in minimal inactivation. Replacement of extracellular Ca by Ba also decreased inactivation. It is concluded that inactivation of the Ca channel is a function of the extent of Ca entry rather than membrane potential, thus differing fundamentally from the purely voltage-dependent mechanism for sodium inactivation.