It has recently been reported that 5% polyethylene glycol 8000 (PEG 8000; Mr 8000) in the diet markedly inhibits the development of colonic tumors in carcinogen-treated rats. To assess the possible use of this agent as a preventive or treatment agent for patients with familial adenomatous polyposis, we determined the effect of PEG 8000 on spontaneous carcinogenesis in the Min mouse. PEG at a 5% concentration in the diet of Min mice did not affect the number of small intestinal or cecal tumors but did increase the number of colon tumors and the number of animals with colonic tumors (2 of 18 versus 12 of 22 animals; P < 0.001). Although the chemopreventive effect of PEG 8000 in rats is remarkable, we suggest a cautious approach in long-term testing of PEG as a chemopreventive agent for subjects at risk for colonic neoplasia.