The presence of antibodies against a dietary protein, bovine serum albumin (BSA), was investigated in the serum of normal subjects and patients with inflammatory bowel disease and celiac disease. Antibodies to BSA were demonstrated in 28 of 30 patients with ulcerative colities (93%), 30 of 35 with Crohn's disease (86%), 5 with untreated celiac disease and in 12 of 28 normal subjects (43%). In patients with inflammatory bowel disease, antibodies to BSA were present in greater amounts in those with severe and moderate disease than in those with mild disease. Moreover, in those patients with high titers of circulating antibody, the serum anti-BSA activity was always associated with IgG and sometimes with IgA. These findings suggest that an increased absorption of antigenic material and stimulation of antibody production may occur in association with intestinal mucosal damage, not only in ulcerative colitis and celiac disease, but also in Crohn's disease.