SUMMARYAssays for islet cell antibodies (ICA) are finding increasing application in clinical diabetology. We have developed a new islet cell antibody assay system (ICA-pA), whose salient features include: (1) utilization of fluorescein-conjugated staphylococcal protein A as a standard second-step reagent, the advantages of this approach being improved "signal" (islet)/"noise" (acini) ratio due to reduction of interfering background acinar pancreatic staining, and facilitation of assay standardization provided by the use of a chemically pure conjugated protein A reagent; (2) monoclonal antibody counterstaining with rhodamine-conjugated BISL-32 for the rapid identification of islets in pancreatic sections; and (3) quantitation of circulating serum ICA by microimmunofluorometric techniques. DIABETES 1985; 34:300-305.A utoantibodies directed against the islet cells of the pancreas are an important hallmark of type I (insulin-dependent) diabetes mellitus. Besides, significance in research studies probing the mechanism(s) of autoimmune beta cell destruction, islet cell antibody assays are currently finding increasing application in clinical diabetology. In particular, recent reports indicate that islet cell antibodies are an important predictive marker of ongoing preclinical beta cell destruction.14 In combination with serial assessments of sensitive indices of beta cell mass/function, like the early-phase insulin release to i.v. glucose, islet cell antibody assays are crucial for monitoring the natural history and chronology of the beta cell destructive