The process of peroxisome proliferation in rodent liver by hypolipidemic compounds and related substances has recently been shown to be receptor-mediated. In the present study, we have examined the effect of oral administration of the strong peroxisome proliferator fenofibrate on the hepatic expression level of the peroxisome proliferator activated receptor (PPAR) in rats. Immunoblots of rat liver cytosols and nuclear extracts using antibodies raised against recombinant PPAR/beta-galactosidase fusion proteins revealed a pronounced increase in the amount of PPAR protein in response to fenofibrate treatment. This induction could also be confirmed at the level of RNA by Northern blotting. A time-course investigation showed a delayed accumulation of mRNA in response to the treatment, starting on day 2 after a latency period of at least one day. Thus, induction of the PPAR as a response to peroxisome proliferators represents one important dimension of the pleiotropic effects of peroxisome proliferators.