Cellular markers are useful in the immunohistochemical studies of normal and pathological tissues. Herein, the development of a monoclonal antibody, Schwann/2E, which reacts with Schwann cells and myelin of the peripheral nervous system (PNS) is described. The Schwann/2E antibody was secreted by a hybridoma of mouse myeloma cells and mouse spleen cells that were immunized in vivo with a cytoskeletal fraction of the human spinal nerve. This antibody immunostained formalin-fixed, paraffin-embedded human, rat, and mouse tissue by the indirect immunoperoxidase method. Schwann cells and myelin of the PNS were intensely labeled by the Schwann/2E antibody. Both the nuclei and cytoplasm of the Schwann cells were labeled. As shown by a comparative light and an electron microscopic study, the Schwann/2E antibody immunoreacted with the Schwann cells that had myelinated axons, but not with those that had unmyelinated axons. The endoneurial fibroblast was not immunolabeled. This antibody slightly stained the endothelial cells of the lung and kidney. Myelin and oligodendroglia of the central nervous system did not react with the Schwann/2E antibody. The Schwann/2E antigen was stable in several histological fixatives. These results indicate that, under normal and pathological conditions, the Schwann/2E antibody could be a useful immunohistochemical marker of Schwann cells and myelin of the PNS.