An increased production of free radicals in the liver has been implicated in a variety of liver diseases. Free radicals can damage cellular macromolecules and, therefore, may participate in hepatocellular injury when produced in excess. Strong evidence exists for hepatic free radical production in animal models of iron and copper overload, ethanol consumption, and ischemia-reperfusion. Although less is known about the situation in humans with liver diseases, the available evidence is consistent with the findings in animal experiments. Treatments that reduce free radical production and/or levels have protective effects in hepatic ischemia-reperfusion. Free radical-initiated lipid peroxidation may play a role in hepatic fibrogenesis, perhaps through an effect of aldehydic peroxidation products on Kupffer cells and lipocytes. This hypothesis is supported by the observation that dietary supplementation with vitamin E has a protective effect on carbon tetrachloride-induced hepatic fibrosis. While cellular damage in human liver diseases is probably multifactorial, free radicals may play important roles in initiating and/or perpetuating this damage.