Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that have been implicated in a variety of biologic processes. The PPARdelta isotype was recently proposed as a downstream target of the adenomatous polyposis coli (APC)/beta-catenin pathway in colorectal carcinogenesis. To evaluate its role in tumorigenesis, a PPARdelta null cell line was created by targeted homologous recombination. When inoculated as xenografts in nude mice, PPARdelta -/- cells exhibited a decreased ability to form tumors compared with PPARdelta +/- and wild-type controls. These data suggest that suppression of PPARdelta expression contributes to the growth-inhibitory effects of the APC tumor suppressor.