We describe a clinicopathological study of a patient presenting with severe and electrophysiological axonal Guillain-Barré syndrome (GBS). An 83-year-old man had a 2-day history of distal acroparesthesias and ascending weakness culminating in quadriplegia, the patient dying 1 month after onset. On day 3, motor conduction velocity (MCV) and distal motor latency values were normal or minimally delayed; most F waves were present with latencies normal or barely delayed. Compound muscle action potential (CMAP) amplitudes were variably reduced. On day 10, there was reduction of CMAPs with relative preservation of MCV. On histological study, the density of myelinated fibers was normal in L5 ventral and dorsal roots, where outstanding lesions included dark fibers, scattered macrophage infiltration, and occasional images of de-remyelination or axonal degeneration. In the fifth spinal nerve, there was widespread loss of myelinated fibers with focal areas showing almost complete fiber loss and variable fascicular combination of extensive de-remyelination and axonal degeneration. Wallerian-like degeneration predominated in femoral and sciatic nerves. Peripheral neuron cell bodies showed central chromatolysis. We conclude that the pathological hallmark of this electrophysiological axonal GBS case is extensive but variable de-remyelination of proximal nerve trunks with superimposed nerve ischemia and axonal degeneration.