Nonsteroidal antiinflammatory drugs may induce apoptosis via inhibition of peroxisome proliferator-activated receptor delta (PPARdelta) activity. Here we analyze the role of PPARdelta in aspirin-induced apoptosis of Jurkat cells, which, together with other lymphoid cell lines, express PPARdelta mRNA. Aspirin increased PPARdelta mRNA levels in Jurkat cells, but decreased the activity of both PPARdelta and PPARalpha/gamma, assayed using the luciferase reporter constructs DRE and ACO, respectively. The DNA binding of PPARdelta was not affected by 10 mM aspirin, which induces apoptosis in Jurkat cells. Moreover, neither addition of a specific ligand of PPARdelta nor transient transfection of PPARdelta expression vectors protected Jurkat cells from aspirin-induced apoptosis. These results indicate that PPARdelta is not involved in aspirin-induced apoptosis. Therefore, the mechanism by which aspirin mediates cell death in Jurkat cells remains unknown.