The purpose of this OPPTS guidance document is to describe the approach the Office will proposes to use to evaluate the scientific information regarding the mode of action of PPAR(alpha) agonists in rodent hepatocarcinogenesis and the relevance of this mode of action for human hepatocarcinogenesis. Other tumor types (e.g. Leydig cell and pancreatic acinar cell tumors) that may be associated with PPAR(alpha)-agonists are briefly described. The document provides an overview of the evidence for a PPAR(alpha)agonist mode of action for liver tumors in rodents, and an overview of all known age and species differences in the key events. Finally, the document will provide guidance in: (1) using a framework to describe and to present the proposed PPAR -mediated mode of action; (2) data needed to demonstrate that rodent liver tumors have arisen as a result of a PPAR(alpha) agonist mode of action; and (3) the relevance of this mode of action for hepatocarcinogenesis in humans. OPPTS will depart from this proposed science policy where the facts and circumstances warrant.