One important cell death pathway involves binding of the cell surface receptor Fas, which recruits and activates specific initiator and effector caspases. In this study Balb/c mice were injected with monoclonal antibody to Fas either alone or followed by the tripeptide caspase inhibitor Z-VAD.fmk. At four hours mice were killed along with concurrent controls and tissues processed for histological examination and immunocytochemical staining for cleaved caspase-3. The livers in all animals treated with Fas alone showed massive apoptosis and positive staining for cleaved caspase-3 whereas those treated with Fas and Z-VAD.fmk or controls showed little or no apoptosis or staining for cleaved caspase-3. These features suggest that massive apoptosis may be important in fulminant liver disease.