Peroxisome proliferator-activated receptor (PPAR) constitutes a subfamily among a large group of ligand-activated transcription factors, the nuclear receptor superfamily. We studied the effects of ligand on the intracellular behaviors of PPAR alpha. Although nuclear localization of PPA-R alpha was not affected by a selective ligand, Wy14643, we observed that exogenously expressed PPARa alpha was rapidly degraded in HeLa cells, and the ligand significantly stabilized the protein. The stability of PPAR alpha was also improved by coexpression of the heterodimer partner retinoid X receptor (RXR) alpha, and further stabilization was not observed with the ligand. These results indicate that PPAR alpha is stabilized through heterodimerization with RXR, and the excess protein unpaired with RXR is rapidly turned over, if not bound by an appropriate ligand. These observations on PPAR alpha are in sharp contrast to the ligand-stimulated degradation reported on PPAR gamma. The ligand-dependent stabilization would have physiological significance when the synthesis of PPAR alpha is elevated exceeding the available level of RXR.