Sensitivity tests of various antiviral drugs on aciclovir-resistant strains of herpes simplex virus type 1 (HSV-1) were done in vitro. Activity of thymidine kinase (TK) of the aciclovir-resistant strains was also investigated. A strain of HSV-1 isolated from a patient with herpes labialis was grown in Eagle's minimum essential medium containing 10(-6)M aciclovir (ACV) and passaged 20 times. Then ACV-resistant strains of HSV-1 were obtained. Sensitivity tests of 5 anti-herpetic agents (ACV, ganciclovir, carbocyclic oxetanocin G, (S)-9- (3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA), and adenine arabinoside (ara-A)) were done on these ACV-resistant strains. The ACV-resistant strains were resistant to ganciclovir and carbocyclic oxetanocin G, but they were sensitive to (S)-HPMPA and ara-A. These ACV-resistant strains showed no detectable TK activity.