The genealogies of 80 patients with IgA nephropathy who were born in central or eastern Kentucky or whose parents were born in this region were researched. At a minimum, 48 of these patients were related to at least one other patient. On the basis of presence or absence of established kinships, the patients were divided into three groups. Twenty-nine patients in group 1 belonged to one large pedigree. Their birthplaces and those of their parents, grandparents, and great-grandparents clustered in the extreme portion of the state. Seventeen other patients, group 2, were related to at least one other patient but not to a patient in group 1. Their birthplaces and those of their ancestors did not show significant clustering. With the exception of two siblings, the 34 patients of group 3 had no family members with IgA nephropathy. The birthplaces for these patients and ancestors were widely scattered. These data suggest that one or more genetically determined factors are important in the pathogenesis of IgA nephropathy in some patients. A founder effect, whereby a gene(s) conveying susceptibility to IgA nephropathy was carried into eastern Kentucky by one or more of the early settlers, would explain the geographic clustering of the birthplaces of the patients in group 1 and their ancestors. The characteristic immunopathology of IgA nephropathy may represent the histologic result of separate disease processes, one or more of which could be genetically influenced.