In order to study B-cell activation patterns independent of T-cell regulation in patients with IgA nephropathy (IgAN), peripheral blood mononuclear cells from 67 patients with IgAN,15 first-degree relatives of patients with familial disease, and 13 normal controls were transformed with Epstein-Barr virus (EBV). Culture supernatants of these transformed cells were assayed for levels of IgG, IgA, and IgM, and results obtained on the three populations were compared. EBV-transformed cells of IgAN patients, as well as the population of first-degree relatives, secreted significantly elevated levels of all three isotypes as compared with the normal controls. However, in comparing ratios of secreted isotypes, it was determined that more IgA relative to IgG and IgM was synthesized by cells of these two populations as compared with the normal controls. Our results imply that (1) the population of B cells susceptible to EBV activation is increased in IgAN patients; (2) this population of “activatable” B lymphocytes is polyclonal and not restricted to the IgA class; and (3) even though there may be a primary B-cell abnormality in IgAN, an additional defect(s) is probably operative in the pathogenesis, since cells of clinically unaffected relatives behaved in a pattern similar to that of patients. © 1991, National Kidney Foundation, Inc.. All rights reserved.