An enzyme-linked immunosorbent assay was developed for differential quantitation of secretory IgA (SIgA) and secretory IgM (SIgM) in human serum. The assay was based on non-competitive binding of SIgA and SIgM to microplates coated with an excess of antibodies to secretory component (SC). Appropriate standards were included to obtain absolute values. Mutual competition of SIgA and SIgM was avoided by testing the serum samples at sufficiently high dilutions. The assay is fast, simple, sensitive and reproducible. All of the 138 healthy individuals tested (1–91 years old) were found to have both SIgA and SIgM in their serum (medians, 10 mg/l and 14 mg/l, respectively). Lactating women, SIgA-deficient healthy individuals, and particularly patients with hepatitis had significantly increased serum SIgM levels compared with controls. Differential quantitation of SIgA and SIgM may turn out to be of diagnostic value and provide pathogenetic information.