Two dammarane saponins, ginsenoside Rb-1 (GRb(I)) and chikusetsusaponin III (Chi III), were investigated for antiviral activity against herpes simplex virus type I using an in vitro plaque elimination assay. Chi III prevented plaque formation at 50 mu M, while GRb1 had no effect at 100 mu M. Chi III was further examined for effects on virus yield and for cytotoxicity. The ID50 value for vines yield reduction was 29 mu M, and cell growth was inhibited by 50% at 66 mu M, indicating that Chi III exhibited marginal antiviral selectivity with a therapeutic index of about 2-fold. Although Chi III exhibited an in vitro virucidal effect with ID50 value of 62 mu M, drug treatment for 24 h reduced an production of the cell-associated virus as,yell as the virus present in the medium, indicating Chi III has intracellular inhibitory activity. Intracellular levels of viral proteins were marginally affected at five hours post-infection, indicating Chi III has a minor impact on the early events of infection.