Concentrations of IgG1, IgG2, and total IgG were measured by a solid phase radioimmunoassay in sera from 36 healthy adults and 114 healthy children. As expected, IgG2 and total IgG had a positive correlation with age in children. In addition to age, several other factors were associated with significant differences in serum subclass concentrations. Female children had higher concentrations of IgG1 than males, and black subjects had significantly higher concentrations of IgG1, IgG2, and total IgG than whites. Although Km(1) and Gm(23) immunoglobulin allotypes had no relation to subclass concentrations when tested as single factors, the Km(1) allotype interacted significantly with race so that Km(1)-positive black children had higher IgG2 concentrations than other subjects. Our findings may explain, in part, recent observations of an association of the Km(1) allotype with altered immune responses of blacks to certain vaccines containing bacterial polysaccharides. In addition, our data indicate the need to control factors such as sex, race, and allotype in studies of subclass concentrations or immune responses.