An attempt was made to detect islet cell surface antibodies (ICSAb) using solubilized islet-cell glycoproteins as antigens. Isolated rat islets were labelled with 125I-wheat germ agglutinin (WGA) and solubilized by Nonidet P-40 with sonication. 125I-WGA-bound islet-cell proteins were incubated with test sera, and bound antibodies were precipitated with anti-human IgG or IgM immunobeads. Serum which had a bound percent beyond the mean plus 2SD of control sera was defined as antibody-positive. Results obtained by this method correlated well with those by the immunofluorescence method of detecting ICSAb. Prevalences of antibodies were 21/114 (18%) for IgG antibodies and 9/114 (8%) for IgM antibodies in patients with insulin-dependent diabetes mellitus (IDDM). The prevalence was highest for both IgG and IgM antibodies in patients within a year of the onset of disease (38 and 25%, respectively), and decreased thereafter. The prevalence of IgM antibodies was lower than that of IgG antibodies at all stages. In NIDDM patients, the prevalence of antibodies was 5/72 (7%) for both IgG and IgM antibodies. If these preliminary results are confirmed, this radioassay may be developed to detect antibodies against islet cell membrane proteins on a large scale.