The distribution of human IgG subclasses among mesangial glomerular deposits of 11 patients with IgA nephropathy (IgA-N) was examined by indirect immunofluorescence with subclass-specific mouse monoclonal antibodies (mAb). A subclass restriction was observed with mesangial deposits containing almost exclusively IgG1 (81% of the studied biopsies) and IgG3 (64%). IgG2 was present in only 1 out of the 11 cases studied and IgG4 was never found to be present, although seven different anti-IgG4 mAb were used. In addition, serum levels of total IgA and IgG, as well as serum IgG subclass levels, were measured in 27 patients with IgA nephropathy by an indirect competitive immunoenzymatic assay using mAb. It was noted in IgA-N patients, but not in normal individuals, that there was significant positive correlation between total IgA and IgG serum levels which was entirely due to a positive correlation between total serum IgA and IgG2 levels. This study provides no explanation for the subclass restrictions observed but suggests that (i) the presence of IgA-IgG1-IgG3 in mesangial deposits may be secondary to an antigenic stimulation, possibly viral, and (ii) the positive correlation between IgA and IgG2 serum levels may result from an increased T helper function.