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 antigens7,8, 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.