We report here that glycyrrhizic acid (GL), a component of licorice root (Glycyrrhiza radix), is active against EBV replication in superinfected Raji cells in a dose-dependent fashion. The IC(50) values for viral inhibition and cell growth were 0.04 and 4.8mM, respectively. The selectivity index (ratio of IC(50) for cell growth to IC(50) for viral DNA synthesis) was 120. Time of addition experiments suggested that GL interferes with an early step of EBV replication cycle (possibly penetration). GL had no effect on viral adsorption, nor did it inactivate EBV particles. Thus, GL represents a new class of anti-EBV compounds with a mode of action different from that of the nucleoside analogs that inhibit viral DNA polymerase.