Monoclonal antibodies to T-lymphocyte subsets and Class II molecules (Ia) have been used to characterize the inflammatory infiltrate in nerve tissue biopsied from 2 patients in the acute phase of Guillain-Barré syndrome; the findings were compared with those in control nerve specimens. Normal control nerve was treated in the same way. In normal nerves, Class II molecules are expressed on endothelial cells and on occasional mononuclear and perineurial cells. In Guillain-Barré nerves the inflammatory infiltrate consisted mainly of Class II-positive cells of the monocyte-macrophage lineage and of lesser numbers of T4 and T8 lymphoid cells. T4 cells predominated in perivascular collections. In the more severely affected patient, there was a marked increase of Class II molecules expressed on endothelial cells, perineurial cells, and most Schwann cells. Schwann cells associated with unmyelinated fibers and the Schwann cell processes of denervated Büngner bands all expressed Class II molecules. These histological changes were less marked in the more mildly affected patient. It is suggested that the expression of Class II molecules on the myelin forming cell, the Schwann cell, has important implications for the pathogenesis of the demyelination that occurs in Guillain-Barré syndrome.