Prior study of coonhound paralysis (CHP) revealed an acute polyradiculoneuritis in raccoon-hunting dogs with clinical and pathologic features resembling those of Guillain-Barré syndrome (GBS). In the present series of five cases, the clinical features were investigated with emphasis on electrodiagnostic and CSF findings, and pathologic changes were evaluated with both the light and electron microscope. The demonstration of motor nerve conduction delay and CSF albuminocytologic dissociation in affected dogs further supported the clinical similarity of CHP and GBS. As in GBS, affected roots and nerves contained mononuclear cell infiltrates, segmental myelin changes and axon degeneration. Despite these general pathologic similarities, the present study suggested that axon damage was a more consistent finding in CHP than in GBS. In contrast to ultrastructural findings in GBS, the demyelinating process in CHP did not appear dependent upon macrophages for its initiation. Swelling, separation and vesiculation of myelin occurred around axons of reduced diameter often in the absence of proximate macrophages. Macrophages, rather than initiating demyelination, appeared to be superimposed on existing damage. In this regard, the observed changes resembled those reported in galactocerebroside-induced EAN and sera-mediated in vivo demyelination.