We demonstrate that glycyrrhizin (GL) enhanced Fas-mediated apoptotic body formation and DNA fragmentation in T cell lines although GL alone did not induce apoptosis. The enhancement effect of Fas-mediated apoptosis by GL was dose-dependent above 0.3 microM. Time course study revealed that simultaneous co-treatment of GL and anti-Fas antibody was crucial for the enhancement of apoptosis and pretreatment with GL was not effective. Anti-Fas antibody elicited caspase-3-like activity. However caspase-3-like activity with co-treatment of GL and anti-Fas antibody was the same level as the antibody alone. Glycyrrhetic acid, the aglycon of GL, did not enhance Fas-mediated apoptosis. The amphipathic property of GL might enable it to interact with the plasma membrane and lead to the enhancement of apoptosis.