Circulating islet cell antibodies (ICA) were present in high frequency (80%) early after diagnosis and decreased in the time course of childhood diabetes mellitus. The complement fixing ability of islet cell antibodies (CF-ICA) in the course of the disease appeared to depend on the titre of ICA: the coefficient of correlation between ICA and CF-ICA titres was 0.79 and all ICA's with a titre over 16 were complement-fixing. Incubating fresh frozen human pancreatic sections thrice rather than once with the children's sera, increased the detectability of complement fixation by a factor 1.4 in all ICA-positive sera. Thus tested, the detection of complement fixation per se did not appear to have a separate pathogenic significance, as the fraction of complement fixing ICA's was almost constant throughout the clinical course. The presence of ICA-IgG subclasses also was dependent on the ICA titre: above a titre of 16 mostly all four subclasses could be detected. Incubating the pancreatic tissue thrice rather than once with ICA-positive sera resulted in enhanced detectability of ICA-IgG1. Early in the course of childhood diabetes, including two prediabetic children, most of the IgG subclasses could be detected in ICA, but after a duration of one year IgG1 alone was mainly seen. In two other children, having a family history of insulin-dependency, restriction to the IgG2 subclass was found.