The presence of significant slowing of motor nerve conduction velocity is considered one of the electrodiagnostic hallmarks of demyelinating neuropathies; however, slowing of conduction velocity may also accompany severe axonal loss. When compound muscle action potential (CMAP) amplitudes are markedly reduced, it is frequently difficult to determine if conduction velocity slowing is due to axonal loss with dropout of the fastest conducting fibers or demyelination. To evaluate the relationship between conduction velocity and axonal dropout, we compared conduction velocities through the same segment of nerve recording from distal and proximal peroneal muscles in patients with chronic neuropathies, in patients with motor neuron disease, and in control subjects. In controls and patients with motor neuron disease, conduction velocities were normal with no significant difference between proximal and distal sites. In patients with axonal neuropathies, conduction velocities were preferentially slowed when recording from distal muscles and relatively normal when recording from proximal sites. Patients with demyelinating neuropathies showed marked slowing of conduction at both sites. We conclude that comparing conduction velocity obtained from proximal versus distal muscle recordings provides a simple, reliable aid for differentiating between chronic axonal and demyelinating polyneuropathies, especially in cases with conduction velocity slowing and low CMAP amplitudes.