IgA deficiency is one of the most common of all immune defects. While it is often not associated with clinical illness, presumably due to compensation from other sectors of the immune system, IgA-deficient individuals are distinctly more likely to become ill and have one or more of specific groups of diseases. While the unifying immunologic perturbation in IgA deficiency is a lack of mature IgA-secreting B cells, a host of other, usually minor, immunologic abnormalities have been reported in such patients. IgA deficiency can be inherited in an autosomal dominant or autosomal recessive fashion, but most individuals who are IgA deficient have no other affected family members. From a genetic point of view, IgA deficiency has been associated with three chromosomes, 18, 14, and 6. Many IgA-deficient individuals who have cytogenically detectable abnormalities of chromosome 18 have been reported, but all the individuals with these defects have severe congenital defects of other kinds. Obscuring the relationship between chromosome 18 and IgA deficiency is the fact that both short- and long-arm deletions have been reported in IgA deficiency. The chromosome deletions in the individuals who are IgA deficient thus appear to have no common pattern. While a rare individual can be IgA1 deficient on the basis of heavy-chain deletions of alpha 1 genes in concert with other heavy-chain genes on chromosome 14, such individuals are quite rare, and from a clinical point of view, those reported have usually been healthy. Absence of both IgA1 and IgA2 genes (presumably in concert with other heavy-chain genes) has never been reported. For chromosome 6, a more complex puzzle emerges. IgA-deficient individuals have been reported to have one of a few specific HLA haplotypes. While many individuals with these supratypes are not IgA deficient, these findings encourage the notion that the secretion of IgA could be at least partly controlled by genes residing in the major histocompatibility locus.