The IgG subclass distribution of autoantibodies to glomerular basement membrane (anti-GBM antibodies) was investigated and compared to the distribution of liver-kidney microsomal (LKM) autoantibodies in chronic active hepatitis, to antimitochondrial autoantibodies (AMA) in primary biliary cirrhosis, and to the subclass distribution of total serum IgG within a healthy population. Solid phase assays for the demonstration of these autoantibodies were performed with four mouse monoclonal antibodies specific for each human subclass to provide quantitative data for the autoantibodies. In addition, the subclass distribution of total IgG in these sera was analyzed. IgGl accounted for 75% of the total antibody activity in anti-GBM antibodies. In LKM antibodies a more homogeneous distribution was observed between the different subclasses with a relative high proportion of IgG4 autoantibodies (21.2%). In AMA a high proportion of IgG3 subclass autoantibodies was found (anti-p-48 = 28.7%, anti-p-62 = 29.9%). In these patients a high proportion of IgG3 (23 vs. 27.2%) could also be demonstrated in the subclass distribution of total IgG, whereas in patients with anti-GBM antibodies and LKM antibodies the subclass distribution of total IgG was comparable to a population of healthy volunteers. We conclude that the subclass distribution in anti-GBM antibodies differs from the distribution in other autoimmune diseases and from a healthy population and that these differences may be of pathogenetic relevance.