The influence of subthreshold depolarizing prepulses on the threshold current-to-distance and the threshold current-to-diameter relationship of myelinated nerve fibers has been investigated. A nerve fiber model was used in combination with both a simple, homogeneous volume conductor model with a point source and a realistic, inhomogeneous volume conductor model of a monofascicular nerve trunk surrounded by a cuff electrode. The models predict that a subthreshold depolarizing prepulse will desensitize Ranvier nodes of fibers in the vicinity of the cathode and thus cause an increase in the threshold current of a subsequent pulse to activate these fibers. If the increase in threshold current of the excited node is large enough, the excitation will be accompanied by a strong hyperpolarization of adjacent nodes, preventing the propagation of action potentials in these fibers. As fibers close to the electrode are more desensitized by prepulses than more distant ones, it is possible to stimulate distant fibers without stimulating such fibers close to the electrode. Moreover, as larger fibers are more desensitized than smaller ones, smaller fibers have lower threshold currents than larger fibers up to a certain distance from the electrode. The realistic model has provided an additional condition for the application of this method to invert nerve fiber recruitment, i.e., real or virtual anodes should be close to the cathode. When using a cuff electrode for this purpose, in the case of monopolar stimulation the cuff length (determining the position of the virtual anodes) should not exceed twice the internodal length of the fibers to be blocked. Similarly, the distance between cathode and anodes should not exceed the internodal length of these fibers when stimulation is to be applied tripolarly.