AbstractPeroxisome proliferators cause increases in liver mass in rodents, linked to changes in cell proliferation and cell death of hepatocytes. These effects are reversible upon cessation of treatment. The underlying mechanism of the response in rodent liver is complex, but clearly dependent on activation of the nuclear receptor PPARα. Other signaling pathways have been implicated in this response, but evidence is mixed. Differing sensitivity among various species to effects of peroxisome proliferators has been associated with differences in PPARα expression and function. Changes in cell proliferation and cell death in neoplastic hepatocytes also have been found in liver tumors caused by long‐term treatment with peroxisome proliferators. Microsc. Res. Tech. 61:179–184, 2003. © 2003 Wiley‐Liss, Inc.