Human herpesvirus 6 (HHV-6) is a recently recognized human herpesvirus isolated from lymphoid cells and thought to be the causative agent for exanthem subitum. Using dot blot hybridization, the HHV-6 sensitivity pattern to several antivirals was compared with those of herpes simplex virus type 1 and human cytomegalovirus. HHV-6 most closely resembled cytomegalovirus in that it was relatively resistant to the antiviral effects of acyclovir and bromovinyl-deoxyuridine but sensitive to ganciclovir and phosphonoacetic acid. From these results, it appears more likely that HHV-6 infections would respond to ganciclovir and foscarnet than to acyclovir should treatment be deemed advisable, although the low toxicity of acyclovir may allow for its use at doses that might affect replication of HHV-6.