A culture of monkey kidney cells (MA-104) resistant to aciclovir (CAS 59277-89-3) was established. The resistant cells were continuously grown in medium containing 200 mumol/l aciclovir whereas normal cells died in such medium. The doses of aciclovir required for 50 and 90% reduction in virus yield were for several Herpes simplex virus Type 1 clinical isolates up to 5-fold higher in resistant than in normal MA-104 cells; in contrast, doses required for 99% reduction in virus yield could be as much as 50-fold higher in the resistant cells. Virus yields developed in the presence of 30 mumol aciclovir in culture medium were at least 10(3)-fold higher in resistant than in normal MA-104 cells. The results showed that the antiviral effect of aciclovir may be significantly decreased in the cell line which developed resistance to aciclovir.