The role of slow potassium current in nerve conduction block induced by high-frequency biphasic electrical current was analyzed using a lumped circuit model of a myelinated axon based on the Schwarz-Reid-Bostock model. The results indicate that nerve conduction block at stimulation frequencies above 4 kHz is due to constant activation of both fast and slow potassium channels, but the block at stimulation frequencies below 4 kHz could be due to either anodal or cathodal dc block depending on the time of the action potential arriving at the block electrode. When stimulation frequency was above 4 kHz, the slow potassium current was about 3.5 to 6.5 times greater than the fast potassium current at blocking threshold, indicating that the slow potassium current played a more dominant role than the fast potassium current. The blocking location moved from the node under the blocking electrode to a nearby node as the stimulation intensity increased. This simulation study reveals that in mammalian myelinated axons, the slow potassium current probably plays a critical role in the nerve conduction block induced by high-frequency biphasic electrical current.