We report a novel prophylactic strategy for peritoneal dissemination and serosal invasion of digestive tract cancer in a murine model, in which the murine abdominal wall was compared to the wall of the human digestive tract. Subcutaneous injection of MH-134 cells to the abdominal wall of C3H mice induced tumors on the parietal peritoneum, and eventually caused peritoneal dissemination with time. In this model, the intraperitoneal administration of OK-432, a type of biological response modifier, after tumor implantation significantly inhibited the development of peritoneal dissemination of tumor cells. This effect was more profound in mice with tumors that extended to the peritoneal surface (designated as S1 stage). Histological examination revealed both the remarkable necrosis of tumoral tissue and the formation of a collagen fiber at the edge of the tumor. This antitumoral effect of OK-432 is thought to be mediated by both macrophages and lymphocytes migrated into the peritoneal cavity, because the administration of Carrageenan and anti-lymphocyte serum completely blocked the antitumoral effect of OK-432.