Sera from 40 Swedish children diagnosed as having Type 1 (insulin-dependent) diabetes mellitus during a one year period along with 40 age and geographically matched control subjects were tested for antibodies to a Mr-64000 islet protein by immunoprecipitation of 35S-methionine-labelled rat islet amphiphilic proteins. Of the 40 diabetic patients, 29 (73%) were found to be positive whereas all 40 control subjects were negative. Samples were also tested for titres of islet cell cytoplasmic antibodies by indirect immunofluorescence on frozen sections of human pancreas. In the diabetic group, 30 of the 40 patients (75%) were positive for islet cell cytoplasmic antibodies compared with 2 of the 40 control subjects (5%). A comparison of levels of antibodies to the Mr-64000 protein with islet cell cytoplasmic antibodies revealed a weak (r s=0.46), but significant (p<0.01) correlation between the two tests. There was no effect of age or sex on levels of antibodies to the Mr-64000 protein. These results in population-based diabetic children and control subjects demonstrate a high frequency of antibodies to the Mr-64000 protein at the time of clinical onset.