Abnormalities in the B lymphocyte population may be relevant to certain altered in vitro immune responses in patients with inflammatory bowel disease. Using a cytofluorometric detection system, we looked for lymphocytes having homogeneous amounts of surface immunoglobulin of only one light-chain class. We studied the peripheral blood lymphocytes from 20 patients with ulcerative colitis and Crohn's disease. Lymphocytes from 12 of 20 patients (60%) with inflammatory bowel disease expressed abnormal light-chain distributions regardless of disease activity, type of disease, or steroid therapy. None of the 15 age-matched normal controls or 12 patients with other intestinal inflammatory conditions showed abnormal light-chain distributions (p greater than 0.01). The data indicate that there are increased numbers of monoclonal lymphocytes in the peripheral blood of some patients with inflammatory bowel disease. One explanation to account for these findings is the possible presence of an abnormality of immune regulation that permits proliferation of such clones.