The serum concentrations of IgM, IgG1, IgG2b, IgG3 and IgA were determined in mice of C57BL/6 background, from weaning to one year of age, by quantitative isotype-specific, indirect double sandwich enzyme-linked immunosorbent assays (ELISAs). Only limited data could be obtained for the IgG2a isotype in the present study. The mean serum Ig levels found for 6-month-old B6 mice were 0.22 mg/ml for IgM, 0.28 mg/ml for IgG1, 1.22 mg/ml for IgG2b, 0.18 mg/ml for IgG3, 0.075 mg/ml for IgA and about 0.7 mg/ml for IgG2a. In comparison with mice of the wild strain, C57BL/6 mice homozygous at the lpr (lymphoproliferation) locus showed very high increases in serum Ig levels when older than 20 weeks. With 6-month-old B6 lpr mice, increases in concentration were found for all tested heavy chain isotypes: 6 to 6.5-fold for IgA (0.45 mg/ml) and IgG1 (1.82 mg/ml), 9-fold for IgG3 (1.6 mg/ml), 11 to 11.5-fold for IgM (2.44 mg/ml) and IgG2b (13.8 mg/ml) and about 8-fold for IgG2a (5.5 mg/ml). Therefore homozygosity at the lpr locus provides the conditions for generalized, poly-isotypic rather than isotype-specific restricted Ig enhancement. This observation may be more compatible with hyperinducibility of all B-cell subclasses than with excessive production of T-cell-derived factors whose activity would be expected to be restricted to some T-dependent subclasses, and at least to affect IgM-committed B cells to a lesser extent than other B-cell classes.