Impaired regulation of immune function may contribute to the abnormal immune responses associated with idiopathic inflammatory bowel disease. We examined the autologous mixed-lymphocyte culture in inflammatory bowel disease patients because this reaction may reflect self regulation of immune responses in vivo and results in activation of suppressor T cells in vitro. We also examined suppressor T-cell generation in two separate assays. In contrast to healthy and disease controls who had normal values, the autologous mixed-lymphocyte culture response was diminished in 44 of 51 (86%) patients with inflammatory bowel disease, independent of disease type, activity, or steroid therapy. Fourteen of 17 inflammatory bowel disease patients (83%) had decreased suppressor T-cell generation. These results show a distinct abnormality in autologous mixed-lymphocyte culture reactivity and in generation of suppressor cells in inflammatory bowel disease. Such impaired immune regulation may be partly responsible for the immunologic aberrations observed in patients with inflammatory bowel disease.