To determine the immunologic and clinical status of individuals from a general population with subnormal levels of IgG2, we prospectively studied 37 of 312 blood donors with low IgG2 levels identified among 8015 donors. We examined (1) G2m(23) allotypes, (2) levels of other IgG subclasses and immunoglobulin classes, (3) composition of peripheral leukocyte populations, (4) responses to two carbohydrate antigen vaccines, (5) in vitro secretion of IgG subclasses by isolated lymphocytes after mitogen stimulation, and (6) clinical histories. We found that most (90%) individuals with subnormal IgG2 levels had G2m(23)- allotypes, whereas only 30% of the unselected donors had G2m(23)-. When individuals were separated according to their G2m(23) allotype, we found that IgG2 "normal" range for individuals with G2m(23)- allotype is 35% lower than for individuals with G2m(23)+ allotype. Individuals who had G2m(23)- allotype and had IgG2 levels ≥0.8 but <1.3 gm/L had no other immunologic abnormalities. In contrast, the individuals with G2m(23)+ allotype and with IgG2 levels <1.3 gm/L and the individuals with G2m(23)- allotype and with IgG2 levels <0.8 gm/L often had additional immunologic abnormalities, including IgA and/or IgG4 deficiency and decreased in vitro expression of IgG2 subclass. None of these individuals had a clinical history remarkable for recurrent infections. Thus, subnormal IgG2 levels interpreted with G2m(23) corrected normal ranges may be a marker of other immunologic abnormalities but taken alone probably have little clinical significance in a general healthy population. © 1990.