Type 1 diabetes arises from the autoimmune destruction of islet β cells, with the participation of both arms of the immune system. To better characterize the β cell membrane, we have raised monoclonal antibodies to the surface of the INS-1 insulinoma cell line. Twenty-two such antibodies were produced, 21 of the IgG class, all reactive to different cell membrane proteins from INS-1 and neonatal islet cells, yielding identical electrophoresis patterns, with molecular weights mainly between 45 and 60kD. We have focused on three such antibodies that recognize different protein targets, and are specific for islet β cells. The target protein of antibody AA4, also found on monkey islets, is expressed at significantly higher levels on β cells (55.8 vs 30.6% of cells, plus 3–4 fold increase in average fluorescence intensity per cell) when neonatal rat islet cells are incubated with high (16mM vs 3mM) glucose concentrations. Further identification of the target antigens is in progress and is expected to shed more light on the properties of β cell membrane proteins, and their probable participation in various disease processes.