Clofibrate and acetylsalicylic and have both been reported to increase carnitine palmitoyltransferase (CPT) activity when administered to rats. The purpose of the present study was to determine the mechanism of the increase in CPT activity. Rats (150-200 g) were fed one of the following: chow, chow with 0.5% clofibrate, or chow with 1% acetylsalicylic acid for 2 weeks. At the end of this time, hepatic CPT activity was increased 4-fold over control in the clofibrate group and 3.6-fold over control in the acetylsalicylic acid group. Immunoreactive protein increased 4.0- and 3.6-fold, respectively, over control. Transcription rates of hepatic nuclei were increased 2.8- and 1.9-fold over control in the clofibrate and acetylsalicylic add groups, and hepatic mRNA levels increased 2.8- and 2.0-fold respectively. These data indicate that increases in CPT activity caused by clofibrate and acetylsalicylic acid administration are due, at least in part, to increased CPT protein, resulting from increased transcription rate and levels of mRNA specific for CPT.