Cancer cells and macrophages produce large amounts of prostaglandin (PG) E2, which suppress cellular immune r action in tumor-bearing individuals. These findings raised a possibility that PG synthetase inhibitor can restore the immune reactivity against tumors. The anti-tumor activity of indomethacin, a potent PG synthetase inhibitor, by oral administration of 0.002% water solution as drinking water from the day 0 or 7 days after tumor transplantation was investigated in BALB/c or CDF1 (BALB/c X DBA/2) mice implanted subcutaneously with colon carcinoma 26 (10(6) cells) as a series of model studies for cancer treatment. The treatment with indomethacin substantially 1) inhibited the tumor growth, 2) prolonged the survival time, 3) caused a regression and disappearance of tumor with some cured mice and 4) reduced the levels of PGE2 and ornithine decarboxylase activity, a first rate limiting enzyme of polyamine synthesis in tumor tissue. Those anti-tumor activities were 5) reduced by a concomitant administration of PGE2 and 6) increased by a combined administration of an immunopotentiating agent, Picibanil (OK-432). The results indicate that indomethacin inhibited the synthesis of PGE2 in the tumor tissue, which suppress the non-specific cellular immune reaction against tumor cells, resulting in the regression and disappearance of tumor. PG synthetase inhibitor may be effective also against human cancer.