IgA nephropathy (IgAN) has been assumed to develop sporadically in individuals. We review the recent clinical and laboratory evidence that supports a genetic influence in the immunopathogenesis in some patients. These data include (1) families with multiple members with the disease not sharing a known nephrotoxic factor, (2) clustering of the birthplaces of ancestors of large pedigrees with multiple affected members, suggesting a “founder effect,” (3) DNA alleles and protein phenotypes associated with IgAN (or a clinical subset) in some patient populations or that cosegregate with the disease in families with multiple affected members, and (4) immunologic abnormalities of patients shared by relatives with renal disease. However, the lack of understanding the fundamental pathogenetic mechanisms hinders progress in the pursuit of genetically controlled process in this disease. Furthermore, the diagnosis requires a renal biopsy, and no therapy has been proven effective. Therefore, asymptomatic family members with IgAN may forego the invasive diagnostic procedure necessary to establish the diagnosis, and instances of familial disease may not be investigated. Nonetheless, the increasing awareness of families with multiple affected members offers an opportunity to investigate the hypothesized genetic influence in the pathogenesis of IgAN. © 1988, National Kidney Foundation, Inc.. All rights reserved.