Peripheral blood mononuclear cells from 18 patients with Crohn's disease were assayed for the activity of indomethacin-sensitive suppressor monocytes. This activity was found to be significantly increased when compared with 16 healthy controls. Patients were also found to have decreased lymphocyte responses to PHA and this impairment correlated with the increased suppression. In contrast, the short-lived suppressor cell activity analyzed simultaneously was found to be decreased as reported in previous studies. Thus, distinct suppressor systems may be differently affected in Crohn's disease and such immunoregulatory aberrations may explain some of the immunological alterations previously reported in Crohn's disease.