Islet cell surface autoantibodies are present in the serum of the spontaneously diabetic BB rat. The availability in large quantities of such autoantibodies should help us understand their significance in vivo. Fusions between BB rat lymphocytes and rat myeloma cells were screened by cellular enzyme linked immunosorbent assay and indirect immunofluorescence on rat living cells. They resulted in a stable hybridoma, called IC2, secreting a monoclonal immunoglobulin M specific for the surface of rat islet cells. This monoclonal antibody was found to bind to the surface of 56% normal rat islet cells and 72% rat insulinoma cells. Protease treatment of rat islet cells resulted in a subsequent 72-100% binding inhibition of IC2 to the surface of these cells, suggesting that IC2 specific antigen is a protein.