The antitumor activity of indomethacin (IND) was investigated in mice bearing advanced colon 26 adenocarcinoma compared with its early transplants. Treatment with 0.001% IND in drinking water retarded the growth of tumor when commenced at Day 1 after the tumor inoculation. The suppression of the tumor growth by IND continued up to 4 to 5 weeks as long as the size of the tumor remained small. On the other hand, IND given to mice bearing a large burden of the tumor at 2 weeks after the inoculation had facilitated the tumor growth. IND reduced tumor-associated PGE2 production in mice bearing either small or large burdens of the tumors. These results indicate that the antitumor activity of IND depends on tumor size and therefore is not simply associated with the reduction of PGE2 levels. We found that colon 26 caused changes in parameters reported for tumor cachexia, such as weight loss, wasting of muscle and adipose tissues and hypoglycemia, when it grew to around 1 g at 2–3 weeks after the tumor inoculation. IND given to the mice with large burdens of colon 26 alleviated the cachexia of the mice, resulting in the increase of the survival time even though the growth of the tumor had been facilitated. It is possible that IND affects the tumor growth and survival by reversing tumor-induced disorders in homeostasis.