The peroxisome proliferator-activated receptor alpha PPAR alpha) is a nuclear receptor that transcriptionally regulates mitochondrial and peroxisomal fatty acid beta -oxidation enzymes in the liver. Ligands include synthetic peroxisome proliferators and some fatty acids. PPAR alpha activation leads to predictable pleiotropic responses in liver including peroxisome proliferation, increased fatty acid oxidation, and hepatocellular carcinoma. In the current study, the response to PPAR alpha -activation was compared in the heart, kidney, and liver since the role of PPAR alpha in extrahepatic fatty acid-oxidizing organs has not been fully explored. Basal expression of mitochondrial beta -oxidation enzymes was comparable in the three tissues, but peroxisomal beta -oxidation enzymes were most abundant in the liver and less so in the kidney and especially in the heart. After PPARa activation with ciprofibrate, both mitochondrial and peroxisomal beta -oxidation enzymes were induced, with the strongest response seen in the liver, a moderate response in the kidney, and no significant response in the heart. PPAR alpha mRNA analysis suggested that the differential response may be related to PPAR alpha expression.