A simple and rapid enzyme-linked immunosorbent assay (ELISA) for the detection of islet cell membrane antibodies (ICMA) in the sera of IDDM has been recently established. This new method has been made possible by using affinity purified islet cell membrane antigens from a monoclonal insulin secreting cell line obtained from a transplantable rat insulinoma (RINm5F). One hundred and thirty-three sera of newly diagnosed diabetic patients (duration of symptoms of less than 3 months) were tested, and ICMA positivity was found in 21% of patients. In the same group we found 64% ICA positive subjects, but no correlation has been found between ICA and ICMA. Therefore these two auto-antibodies should be considered as expression of different steps of the autoimmune beta-cell damage. In this light ICMA could represent a very early marker of autoimmune process and it could be useful to recognize, among risk subjects, those who are developing IDDM.