The mechanisms of nerve conduction block induced by high-frequency biphasic electrical currents were investigated using a lumped circuit model of the myelinated axon based on Frankenhaeuser-Huxley (FH) model or Chiu-Ritchie-Rogart-Stagg-Sweeney (CRRSS) model. The FH model revealed that the constant activation of potassium channels at the node under the block electrode, rather than inactivation of sodium channels, is the likely mechanism underlying conduction block of myelinated axons induced by high-frequency biphasic stimulation. However, the CRRSS model revealed a different blocking mechanism where the complete inactivation of sodium channels at the nodes next to the block electrode caused the nerve conduction block. The stimulation frequencies to observe conduction block in FH model agree with the observations from animal experiments (greater than 6 kHz), but much higher frequencies are required in CRRSS model (greater than 15 kHz). This frequency difference indicated that the constant activation of potassium channels might be the underlying mechanism of conduction block observed in animal experiments. Using the FH model, this study also showed that the axons could recover from conduction block within 1 ms after termination of the blocking stimulation, which also agrees very well with the animal experiments where nerve block could be reversed immediately once the blocking stimulation was removed. This simulation study, which revealed two possible mechanisms of nerve conduction block in myelinated axons induced by high-frequency biphasic stimulation, can guide future animal experiments as well as optimize stimulation waveforms for electrical nerve block in clinical applications.