We studied the sensitivity of human herpesvirus-6 (HHV-6) to 4 antiviral drugs known to be effective in the treatment of infections with other human herpesviruses and human immunodeficiency virus. HHV-6 was grown in peripheral blood lymphocytes, and virus multiplication was quantified by evaluation of the cytopathic effect by molecular hybridization and indirect immunofluorescence assay. The 50% and 90% inhibitory concentrations (IC50 and IC90) were determined for each drug. The results obtained by the 3 different quantification techniques were found to correlate, and enabled us to conclude that HHV-6 replication was readily inhibited by foscarnet or ganciclovir. In contrast, inhibition of HHV-6 replication was observed only at high concentrations of acyclovir, and was not detected at the tested concentrations of zidovudine.