The systemic immune response to a booster dose of attenuated polio vaccine has been studied in a group of patients with IgA nephropathy, their parents and healthy unrelated controls. The serum IgA and IgG antibody response and the antibody response in cultured lymphocyte supernatants was quantitated by a sensitive radio-immunoassay. Three of eight patients and two of their parents had elevated serum IgA antibody to polio pre-immunization. There was no significant rise in serum IgA or IgG antibody to polio post-immunization in any group. However, the five subjects with elevated pre-immunization levels fell into the normal range post-immunization, suggesting IgA specific suppression. Total and antigen specific IgA rose post-immunization in culture supernatants in all groups. The rise did not differ among the groups. The patients and parents with high serum antibody also had high culture supernatant levels and these fell post-immunization. There was an increased antigen non-specific IgG response in four patients and three of their parents. The data provide additional in vivo evidence of an upregulated IgA immune response in patients with IgA nephropathy. In addition, the data provide the first in vivo evidence of aberrant immune responses in the first degree relatives of patients with IgA nephropathy. This appears to be one of perhaps several inherited traits which may predispose an individual to develop this common and progressive nephropathy.