In Guillain-Barré syndrome patients, severe axonal degeneration occasionally occurs, often resulting in permanent functional deficit. In order to assess the development of axonal degeneration, we followed a consecutive series of 42 patients longitudinally using clinical and neurophysiological methods. Eight patients were considered to have severe axonal degeneration: in these patients denervation potentials were eventually found and at least 1 nerve proved inexcitable, and clinical recovery was slow and incomplete. Five of these 8 patients initially showed a pronounced generalized conduction block, the physiological hallmark of demyelination, before signs of axonal degeneration developed. In the remaining three patients, the first evaluation revealed low amplitudes with only modest conduction block; this is consistent with predominantly distal demyelination, but might, alternatively, be explained by primary axonal degeneration. Caution is necessary in using distal CMAP parameters for prognostic purposes, because the distal CMAP may be relatively spared in the early phase of the disease despite severe axonal degeneration later.