Abstract: Resistant variants of HSV-1 wt stain to ACV, CC, DHPG and PFAcan be selected after several passages in drug-containing cultures. The degree of resistanceof different variants varied and emerged at different times. The combination of antiviralagents can delay and even prevent the emergance of drug-resistant variants. At the sametime, the concentration, dose and, therefore, toxicity of the antiviral agents can also be re-duced. So, it is a feasible method for treating resistant HSV infections. Cross-sensitivitytests showed that ACV^r variants are resistant to ACV, DHPG and PFA, but sensitive toCC; PFA~r variants are sensitive to ACV, CC and DHPG; CC^r variants are sensitive toACV and DHPG, but resistant to PFA; DHPG^r variants are sensitive to ACV, CC andPFA, These results suggest that the study of cross-sensitivity of HSV strains in vitro pro- vide information which will aid the design of sultable therapy for drug-resistant HSV in-fections.