Although PROb colonic tumor cells are immunosuppressive, the immunomodulator OM 163 induced the disappearance of macroscopic peritoneal nodules in 50% of rats bearing a peritoneal carcinomatosis (p.c.) induced by PROb cells. When the p.c. developed, the number of T lymphocytes was low and the expression of interferon (IFN)-gamma mRNA in tumor nodules decreased very rapidly. The TGF-beta 1 secreted by PROb cells could be responsible for the immunosuppression, because the PROb cell supernatant inhibited IFN-gamma production and T lymphocyte proliferation. When the rats were treated with OM 163, an infiltration of T lymphocytes was observed in tumor nodules, as well as a high expression of the IFN-gamma mRNA. The antitumor efficiency of the immunomodulator OM 163 could be explained in part by a direct effect of OM 163 on T lymphocytes, because in vitro it stimulated the proliferation and the secretion of IFN-gamma of T lymphocytes. OM 163 could also act at the TGF-beta 1 level. Although OM 163 alone or in combination with IFN-gamma did not modify the TGF-beta 1 secretion by PROb cells in vitro, the expression of the TGF-beta 1 mRNA and the TGF-beta 1 protein content was decreased in vivo in treated tumor nodules.