Patients with IgA nephropathy have elevated serum levels of polymeric IgA, probably due to an increase in their synthesis by peripheral blood mononuclear cells, and specific abnormalities in the immunoregulation of IgA. The existence of familial cases of IgA nephropathy, as well as the published association of this nephropathy with some antigens of the HLA system, decided us to test the hypothesis that some of these alterations might be genetically controlled. For this reason we studied some of these immunological assays in 25 first-degree relatives of 7 patients with IgA nephropathy and 22 control subjects matched for age and sex. An abnormal immunological assay was found in at least 1 relative of all families examined. Thus, 16 of 25 relatives had a significant increase in the percentage of polymeric IgA-producing cells after 7 days of culture in the presence of pokeweed mitogen. Some derangement in the concanavalin A generation of specific IgA suppressor cells was found in 11 out of 25 relatives. These results are, though in lower frequency, similar to those seen in patients and suggest that the IgA-immunological abnormalities observed are genetic markers, even if they cannot by themselves explain the pathogenesis of the IgA nephropathy. The absence of IgA immune complexes seen in relatives as well as their high prevalence in patients suggest that in predisposed subjects other factors (genetic or not) are required for the development of IgA nephropathy.