Two-color immunofluorescence staining in situ demonstrated increased proportions of immunoglobulin A2 subclass-producing cells in jejunal mucosa from adult patients with untreated (47%, P < 0.01) or treated (37%, P < 0.05) celiac disease compared with controls (28%). Costaining was also performed for joining chain, which is a key factor in the epithelial transport of secretory antibodies; its expression by immunoglobulin A2 cells was only marginally reduced in untreated patients (96%) compared with treated patients and controls (98%). Also, immunoglobulin A1 cells showed similar joining chain positivity (89%) in all three groups. Considering the expanded total jejunal immunoglobulin A-cell population and the subclass-associated joining chain expression, it could be calculated that the potential of immunoglobulin A2 cells for contribution to secretory immunity was increased 3.9 times in untreated (P < 0.01) and 1.8 times in treated (P < 0.05) patients and that of immunoglobulin A1 cells was increased 1.7 times in untreated (P < 0.05) but remained unaltered in treated patients. The estimated relative contributions of locally produced immunoglobulin A2 to secretory immunoglobulin A would thus be 51% and 37% in the two patient categories, respectively, compared with 31% in the controls. These data suggested enhanced secretory immunity in celiac disease and might reflect a protective, possibly antimicrobial, immune response. It could not be excluded, however, that increased generation of secretory immunoglobulin A at the same time contributes to the gluten-induced pathogenesis of celiac disease.