A rapid and sensitive assay was developed to analyse the sensitivity of wild type HSV-1 and HSV-2 isolates with respect to a battery of antiviral substances. In the viral sensitivity assay, human embryonic lung fibroblasts are incubated with the virus isolate and different concentrations of the antivirals. After 1-3 days, the cells are disrupted and analysed for HSV type 1 or 2 antigens by an enzyme-linked immunosorbent assay. Antigens corresponding to 17 plaque-forming units were detectable after 1 day of incubation. After 3 days, HSV antigens derived from less than one plaque-forming unit were measurable. The sensitivities of 22 HSV-1 and 19 HSV-2 primary isolates from untreated patients were tested against adenosine arabinoside, acyclovir, phosphonoformic acid and iododeoxyuridine. Each isolate was found to have an individual pattern of sensitivities to the different antivirals. Five isolates were judged to be relatively resistant to one or more of the drugs tested.