We investigated the in vitro immunosuppressive effect of the sera and the culture supernatants of the peripheral blood mononuclear cells obtained from patients with Crohn's disease. Sera from Crohn's disease markedly suppressed the proliferative response of mouse spleen cells, compared with sera from ulcerative colitis, intestinal tuberculosis and normal controls. The culture supernatants of the adherent mononuclear cells from Crohn's disease showed a remarkable suppressive effect (96 +/- 1%), while the culture supernatants of the non-adherent mononuclear cells had no suppressive activity (-10 +/- 16%). The culture supernatants of the adherent and non-adherent mononuclear cells from normal controls had no suppressive activity. The fractionization of the culture supernatants of the adherent cells from the Crohn's disease patients demonstrated that the fractions with high suppressive activity had similar or identical biochemical properties to the serum immunosuppressive fractions which has been reported previously. These results indicate that monocytes may release the serum immunosuppressive factor in Crohn's disease. This factor may contribute to the depression of the immune reactivity in the mucosal lesion and to the persistence of the stimulation of abnormal immune response in the intestinal wall.