The effectiveness of acycloguanosine (acyclovir) and trifluorothymidine (TFT) as inhibitors of cytomegalovirus (CMV) infection was tested using a plaque-reduction assay. Two laboratory strains and seven clinical isolates were employed. The results indicated that both acyclovir and TFT were ineffective in inhibiting viral cytopathic effect (CPE) below the concentration of 50 microM. At concentrations of 100 microM or more, greater than a 50 percent inhibition was achieved by both acyclovir and TFT on all clinical isolates. Although complete inhibition of plaque formation was seldom achieved even at a drug concentration as high as 200 microM, a reduction of plaque size was consistently observed at drug concentrations above 100 microM. When a low dose of virus was used for infection, ED50 could be achieved at an acyclovir concentration of 50 microM. Laboratory strains of CMV were found to be more resistant than the clinical isolates to inhibition of acyclovir.