We studied the role of antiganglioside antibodies in the pathogenesis of autoimmune neuropathies using an in vitro preparation of a rat sciatic nerve. Human and rabbit sera with high titers of the antibodies were applied to a restricted segment of the sciatic nerve mounted in a recording chamber, and the compound nerve action potentials of the myelinated and unmyelinated fibers were observed. Myelinated fiber conduction became blocked at the segment within a few hours, whereas the unmyelinated fiber conduction remained unchanged. These results suggest that antiganglioside sera directly produce an acute conduction block only in myelinated nerve fibers and that this in vitro model is useful for studying the ionic mechanism by which the acute conduction block occurs.