The Min mouse provides a genetically defined model for inherited and sporadic forms of human colorectal tumorigenesis. To test the suitability of this model for the evaluation and optimization of chemopreventive agents, we examined the effects of sulindac on tumorigenesis in Min mice as this compound can inhibit colorectal tumorigenesis in human familial adenomatous polyposis patients. Treatment of Min mice with sulindac in their drinking water (84 mg/l) or diet (167 and 334 p.p.m.) resulted in a significantly decreased average tumor load. The conservation of sulindac activity in the Min mouse provides an opportunity to explore the mechanism of sulindac suppression as well as to test other potential chemopreventive agents.