Utilizing defined monoclonal antibody reagents, the immunoglobulin class and subclass distribution of human islet cell antibodies (ICA) were evaluated by means of an indirect immunofluorescence technique. ICA positive sera from 14 subjects with Type 1 diabetes and 10 with "Pre-Type 1 diabetes mellitus" (ICA positive, currently non-diabetic "high risk" subjects, mostly first degree relatives, with varying degrees of beta cell dysfunction) were analyzed. ICA were confined solely to the IgG class, the majority of the subjects (17/24) demonstrating an ICA response restricted to one IgG subclass only (IgG1). The remainder (7/24) showed an IgG subclass distribution extending to no more than 2 subclasses only (IgG1 + IgG2 or IgG1 + IgG3). There was no relationship between specific ICA-IgG subclass response and the age, sex, stage and duration of diabetes mellitus. An ICA-IgM response was not seen in any of the subjects, including those studied during the early preclinical phase of insulin-dependent diabetes mellitus.