To trace sites for local complement activation in inflammatory bowel disease, an indirect two-colour immunofluorescence method was applied on prewashed and directly ethanol-fixed mucosal specimens from patients with ulcerative colitis, Crohn's colitis, or terminal ileitis. Monoclonal antibodies to the IgG subclasses and to neoepitopes of activated complement C3b and the terminal complement complex (TCC) were used in combination with rabbit antiserum to immunoglobulins and various complement components. Deposits of activated C3b were found on the luminal face of the surface epithelium in the most affected ulcerative colitis specimens from 91% of 23 studied patients, together with cytolytic TCC in 81%. Furthermore, there was a selective deposition of the immunoglobulin G subclass 1 (IgG1) within the epithelial immune complexes in 63% of 11 studied patients. These results suggested that IgG1 autoantibodies to brush-border antigen(s) induce a complement-mediated attack on the epithelium in ulcerative colitis. The epithelial complement deposition seen in Crohn's disease tended to be more granular and was observed in 5 of 10 patients with colitis and in 4 of 10 with ileitis. No co-localization of IgG was observed, suggesting that complement activation had been induced by the alternative pathway. Type III immune reaction may, in addition, take place in both diseases since there was evidence of continuous vascular complement activation in submucosal blood vessels.