Insulin-dependent diabetic (IDD) patients have a high prevalence of circulating autoantibodies against islet of Langerhans cells at the time of diagnosis1-4. Inflammatory cells within the islets5, leukocyte migration inhibition in response to pancreatic antigens6 and an association with certain HLA-D/DR histocompatibility antigens 7,8, have also been observed. It seems that the autoantibodies may be pathogenically relevant as they react primarily with β-cells9, but the specific target antigen(s) have yet to be identified. In the present study we determined whether sera from insulin-dependent diabetic children are able to immunoprecipitate proteins from detergent lysates of human islet cells. We report that sera from 8 out of 10 newly diagnosed diabetic children consistently immunoprecipitate a protein having a molecular weight (M r) of ∼64,000 (64K). An additional protein (38K) was precipitated from islet cells obtained from a HLA-DR3-positive donor. Neither of the proteins was precipitated by non-diabetic sera nor detected in immunoprecipitates from human lymphocyte lysates. It is suggested that the 64K and/or 38K protein components may represent cell-specific target antigens in insulin-dependent diabetes.