The development of IgA nephropathy in first degree relatives is a well-described, yet relatively uncommon, occurrence. The association of a C4 isotype deficiency or partial deficiency of another complement protein has been previously documented for patients with IgA nephropathy. The present report describes a family in which two siblings and their father had biopsy-confirmed IgA nephropathy; both siblings were deficient for the C4B isotype. In addition, one of the biopsied siblings and a third sibling with microscopic hematuria but no renal biopsy apparently had a partial deficiency of the complement regulatory protein, I. The findings in this family may be compatible with the hypothesis that a C4 isotype deficiency and/or a partial deficiency of an individual complement protein allows clinical expression of IgA nephropathy in an individual with a genetic susceptibility for the disease. © 1990, National Kidney Foundation, Inc.. All rights reserved.