In 28 patients with Crohn's disease, 6 patients with ulcerative colitis, and 34 healthy controls, immunoregulatory function of peripheral blood mononuclear cells was investigated by evaluating the suppression of lymphocyte proliferative responses to mitogens (phytohemagglutinin, concanavalin A, pokeweed mitogen) and to allogeneic lymphocytes (mixed lymphocyte culture) using simultaneously five functional assays as follows: (a) spontaneous T-suppressor-cell activity, (b) concanavalin A-generated T-suppressor-cell activity, both with (3000 rads) and without irradiation of suppressor cells, and (c) allogeneic mixed lymphocyte culture-generated T-suppressor-cell activity, again both with and without irradiation. Concanavalin A- and mixed lymphocyte culture-generated T-suppressor-cell activities were evaluated both in the autologous and the allogeneic system. In addition, using monoclonal antibodies, we determined proportions of T-helper and T-suppressor/cytotoxic lymphocytes. Inactive patients did not differ from normal either in the proportions of immunoregulatory lymphocytes or in the suppression of the various lymphocyte proliferative responses in any of the five T-suppressor-cell assays evaluated. In patients with active disease, however, an impairment of suppression of phytohemagglutinin-, pokeweed mitogen-, and mixed lymphocyte culture-stimulated proliferation of autologous lymphocytes was observed in the concanavalin A-generated, irradiated suppressor assay. In the spontaneous suppressor assay, suppression of phytohemagglutinin- and concanavalin A-stimulated lymphocyte proliferation was significantly lower in active disease than in remission. Thus, in peripheral blood of patients with Crohn's disease who are in remission, there is no indication for an immunoregulatory defect in any of the evaluated assay systems. Single selective, moderate defects in suppression of proliferation of various lymphocyte subpopulations are restricted to active disease.