Exposure to formaldehyde appears to be associated with hepatoxicity in many species, including humans, following injection, ingestion, or inhalation. Macroscopic, microscopic, and biochemical manifestations in the liver include alterations in weight, centrilobular vacuolization, focal cellular necrosis, and increased alkaline phosphatase concentrations. Time-related changes in the pattern of the effects are suggested as one goes from acute exposure by inhalation at greater concentrations to repeated exposure at lesser concentrations. Although the hepatic changes are generally not extensive and can be reversible following acute exposure, the potential exists for them to progressively become more serious with repeated exposures. There are several possible mechanisms for the toxicity. Depending on the route of exposure could include direct effects on hepatocytes and/or indirect effects through the circulatory and immune systems. The catabolism of formaldehyde includes conversion to CO2 by reactions involving glutathione. Many hepatotoxic chemicals require glutathione for detoxification. Formaldehyde may then have the potential to cause additive toxicity with such chemicals in some circumstances.