Antidromic cortical excitation has been implicated as a contributing mechanism for high frequency deep brain stimulation (DBS). Here, we examined the reliability of antidromic responses of type 2 corticofugal fibers in rat over a stimulation frequency range compatible to the DBS used in humans. We antidromically activated single layer V cortical neurones by stimulating its two axonal branches. We found that antidromic cortical excitation is not as reliable as generally assumed. Whereas the fast conducting branches of a type 2 axon in the highly myelinated brainstem region follow high frequency stimulation, the slower conducting fibers in the poorly myelinated thalamic region, function as a low pass filters. These fibers fail to produce consecutive antidromic spikes at the beginning of high frequency stimulation, but are able to maintain a steady low-frequency (6-12 Hz) spike output during the stimulation. In addition, antidromic responses evoked from both branches are rarely present in cortical neurones with a more hyperpolarized membrane potential. Our data indicates that axon-mediated antidromic excitation in the cortex is strongly influenced by the myelo-architecture of the stimulation site and the excitability of individual cortical neurones.