1. Voltage clamp experiments were carried out on squid giant axons which were perfused internally with 300 mM-NaF + sucrose and placed in K-free artificial sea-water at 16-17 degrees C. On stepwise depolarization (V = -38.5 to 68 mV) the Na conductance g(Na) rapidly reached a peak value and then declined to a new level; this ;maintained' level was slowly inactivated in an exponential manner with a rate constant which varied from 0.3 to 1.1 sec(-1). This process was not influenced appreciably by replacing 50 mM-NaF with KF.2. On repolarization to a potential which varied between -73 and -101 mV the slow inactivation was removed with a rate constant of 0.11-0.73 sec(-1).3. Prolonged depolarization also produced a slow inactivation of the ability of the membrane to give a transient increase in g(Na). This effect developed at a rate about (1/3)-(1/2) that associated with the inactivation of the ;maintained' component; on repolarization, recovery of the peak g(Na) was 1-2 times as fast as recovery of the ;maintained' g(Na).4. In experiments on fibres perfused with 300 mM-KF after internal NaF had removed the usual delayed K conductance, depolarization resulted in an outward current which developed in an exponential manner with a time constant of a fraction of a second. The equilibrium potential for this component was more negative than -50 mV.5. Long-lasting action potentials were computed on the basis of the above slow changes and, except for the period of final repolarization, were found to be in satisfactory agreement with experimental records. The discrepancies suggest that there may be additional slow changes in permeability which could not be resolved in the present experiments.