The mechanisms by which peroxisome proliferators are able to regulate metabolic processes such as fat metabolism, whileat the same time creating an environment for the development of hepatocellular carcinomas, is a central issue in the non-genotoxic carcinogenesis field. The convergence of two members of the steroid receptor family (peroxisome proliferator-activated receptor, PPAR; and retinold X receptor, RXR) has provided strong support for an oxidative stress component in this carcinogenesis process, but has yet to define clearly a pathway for the classical tumor promotion events associated with peroxi-some proliferation. The findings presented here integrate a third member of the steroid receptor family into this process and suggest a novel autocrine loop and mechanism for creating both oxidative stress and tumor promotion. A central regulatory component in this pathway is farnesol which has recently been shown to induce transcription mediated by the steroid receptor family member, farnesoid X receptor (FXR). In this report, it is clearly demonstrated that farnesol can also upregulate the transcriptional events of PPAR, but most likely through a different farnesoid metabolite, resulting in the regulation of an entirely different set of genetic components. Deregulation of the activities of these receptors offers a provocative mechanism for explaning the hepatocarcinogenic effects of peroxisome proliferators in chronically treated rodents.