The effects of monovalent internal cations Cs+, Li+ and Na+ on potassium channel conductance in the frog node of Ranvier were studied by means of the voltage clamp. As previously reported, when 10-80% of the internal K+ was replaced by one of the above cations, the steady-state current-voltage relationship was significantly modified. The main effect was a voltage-dependent attenuation of the currents. We demonstrate that the current attenuation is associated with a change in the channel gating kinetics. For small depolarizations the kinetics can be described by the usual potassium conductance activation time constant, tau n. However, under certain experimental conditions (e.g. substitution of the intracellular K+ with 10% Cs+), during larger depolarizations, stepping the membrane potential to values above 40-60 mV, the conductance develops with two time constants: tau n and a new, slower time constant that, in contrast to tau n, grows with membrane potential. These results can be explained by assuming that the cations may occupy two different sites in the channel; when the first site is occupied the channel is blocked, while occupation of the second site results in slowing of the gating kinetics in the affected channels.