To understand the relevance of subnormal serum concentrations of IgG2, we measured IgG2 in serum of 575 healthy children and identified 11 with concentrations > 2 SD less than the mean for age. The levels of IgG2 present were similar to those found in symptomatic children with IgG2 subclass deficiency associated with antibody deficiency. The 11 children ranged in age from 1 to 14 y (mean=5.7). Detailed clinical information was available on 10 of the 11 children and each was matched for age with two controls. The median number of visits/y to the doctor for infectious illnesses was identical for the two groups (1.0). Nine of the children with subnormal IgG2 were followed for 1 to 5 y (mean=2.3). All nine children had normal serum concentrations of IgA, IgGl, IgG3, and IgG4 but seven had persistently subnormal or low-normal serum IgG2 concentrations. One of these seven children also had a subnormal serum concentration of IgG, and one had subnormal IgM. Antibody responses to Haemophilus b polysaccharide vaccine were normal in five of six who were immunized. In vitro secretion of Ig by mitogen-stimulated peripheral blood mononuclear cells was measured in six of seven children with persistently subnormal or low-normal IgG2; five showed decreased secretion of IgG2, and two of the five also had subnormal secretion of IgGl and IgG3. An important implication of this study is that the subnormal concentrations of serum IgG2 found in infectionprone children are not a sufficient explanation for their increased susceptibility to infection. The healthy children with low serum concentrations of IgG2 differ from symptomatic children with subnormal IgG2 in that the former have otherwise normal serum Ig concentrations and have normal antibody responses to Hib PS vaccine.