Inhibition of type-1 herpes simplex strains resistant to acyclovir, phosphonoacetic acid and their combination by combined use of three drugs with different mechanisms of action capable of suppressing reproduction of the acyclovir resistant strain was studied. The combinations used were the following: Ara-A + ribavirin + phosphonoformic acid, Xylo-A + ribavirin + phosphonoformic acid and Ph-ACH + Ara-A + ribavirin. The former two combinations had a synergistic action on the standard strain L2 whose drug susceptibility had not undergone changes as well as on the acyclovir resistant strain. As for the strain resistant to phosphonoacetic acid and to acyclovir + phosphonoacetic acid the effect was additive. Ph-ACH + Ara-A + ribavirin had a marked synergistic action on all the strains tested.