In addition to the well-known T-cell dysfunctions in AIDS, hypergammaglobulinemia, mostly IgG, and autoimmune phenomena indicate that B cells are also involved. Reports of HIV-infected and activated B cells suggest T cell-independent B-cell abnormalities. In order to assess the IgG subclasses involved in hypergammaglobulinemia, we examined all four IgG subclasses in sera and in vitro with an enzyme-linked immunosorbent assay (ELISA). The in vitro studies included 7-day cultures of mononuclear cells and highly purified B cells stimulated with a T cell-independent polyclonal B-cell activator (Klebsiella pneumoniae, KlebsM). Cultures were done with cells from seven patients with AIDS, seven patients with persistent generalized lymph node enlargement and HIV antibodies, and normal controls. In vivo, hypergammaglobulinemia was found to be restricted to the IgG1 subclass. In vitro, high spontaneous levels of IgG were not elevated significantly under stimulatory conditions, as demonstrated by the measurement of all four IgG subclasses in the culture supernatants. In vitro, hypergammaglobulinemia also resulted from IgG1. These results indicate that there are B-cell abnormalities in pre-AIDS and AIDS, in that the B-cell preactivation in vivo resulting in hypergammaglobulinemia is restricted to IgG1.