The nature ofthe permewablity change8 At present the thickness and composition of the excitable membrane are unknown. Our experiments are therefore unlikely to give any certain information about the nature of the molecular events underlying changes in perme-ability. The object of this section is to show that certain types of theory are excluded by our experiments and that others are consistent with them. The first point which emerges is that the changes in permeability appear to depend on membrane potential and not on membrane current. At a fixed depolarization the sodium current follows a time course whose form is independent of the current through the membrane. If the sodium concentration is such that ENaB< E, the sodium current is inward; if it is reduced until ENa> E the current changes in sign but still appears to follow the same time course. Further support for the view that membrane potential is the variable controlling permeability is provided by the observation that restoration of the normal membrane potential causes the sodium or potassium conductance to decline to a low value at any stage of the response. The dependence of 9Na and g9 on membrane potential suggests that the permeability changes arise from the effect of the electric field on the distribu-tion or orientation of molecules with a charge or dipole moment. By this we do not mean to exclude chemical reactions, for the rate at which these occur might depend on the position of a chargedsubstrate or catalyst. All that is intended is that small changes in membrane potential Would be most unlikely