With increased viral infections in immunocompromised patients because of cancer therapies, organ and bone marrow transplantation, and HIV infection, the use of antiviral therapeutics has increased. Consequently, antiviral resistance has developed. As the incidence of antiviral resistance increases, the need for a simple and rapid method to determine the susceptibility of a virus becomes more important. To develop such a method, we first examined the use of tissue cultures inoculated with viral suspensions and incubated in the presence of various concentrations of antiviral agents. An enzyme immunoassay was used to detect viral growth, which subsequently determined an infecting dose 50, indicating susceptibility or resistance. Other efforts involved adaptations of the plaque- reduction assay using monoclonal antibody staining of infected cell monolayers to obtain rapid susceptibility results. None of the methods investigated enabled unambiguous assessment of the effects of the antiviral agents tested. Interpretation of results was further complicated by the lack of a recognized reference method, as well as by the lack of standard guidelines for antiviral susceptibility testing. Hence, it does not seem feasible at this time to continue to develop a rapid viral susceptibility testing procedure for routine laboratory use.