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1. Single myelinated nerve fibres were isolated and the nodal currents were recorded under potential clamp conditions. The effect of membrane potential on the Na permeability (PNa) mechanism was analysed. 2. The available PNa increased slowly during negative polarization of the membrane. The time course of this change was about 10(3) times slower than the time course of the mechanism for the usual PNa inactivation (h-system). The slow PNa changes could be distinguished from changes in h because of the difference in rate. 3. The slow PNa variation was independent of the state of the h-system and was largely due to a slow inactivation system, which empirically could be described as separate from the other permeability variables. 4. In the steady state the slow inactivation appeared almost absent at a holding potential of -120 mV, whereas it was 30% complete at the resting potential (-70 mV) and 80% complete at a holding potential of -20 mV. 5. Changes in the slow inactivation system showed an approximately exponential time course. At 10-12 degrees C the time constant was about 3 sec with U = -70 mV, 7 sec with U = -100 mV and 1-5 sec with U = -127 mV. 6. High Ca shifted the steady state slow inactivation curve in the positive direction along the potential axis.

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