Targeting of the nuclear prostaglandin receptor peroxisome proliferator-activated receptor δ (PPARδ) by homologous recombination results in placental defects and frequent (>90%) midgestation lethality. Surviving PPARδ^−/− mice exhibit a striking reduction in adiposity relative to wild-type levels. This effect is not reproduced in mice harboring an adipose tissue-specific deletion of PPARδ, and thus likely reflects peripheral PPARδ functions in systemic lipid metabolism. Finally, we observe that PPARδ is dispensable for polyp formation in the intestine and colon of APC^min mice, inconsistent with its recently proposed role in the establishment of colorectal tumors. Together, these observations reveal specific roles for PPARδ in embryo development and adipocyte physiology, but not cancer.