Major advances have been made in the treatment of herpesvirus infections in the compromised host. Acyclovir is clearly effective in the treatment of HSV infection, and preferable to vidarabine for this purpose. Additional information about the optimal use of acyclovir for treatment or prophylaxis and about the ultimate significance of the phenomena of acyclovir resistance and possible suppression of the specific immune response are needed. The major challenge at this time is the rapid clinical or virologic diagnosis of HSV infection, especially the rarer manifestations such as HSV pneumonia or encephalitis, so that effective therapy can be initiated. The serious manifestations of VZV infection (e.g. cutaneous and visceral dissemination) can also be controlled with either vidarabine or acyclovir, although definition of the agent of choice is still lacking. More information is needed to define the relative efficacy of acyclovir compared with vidarabine, and also to define better treatment regimens for the prevention of post-herpetic neuralgia which remains a major source of morbidity. Use of either oral or topical acyclovir and anti-inflammatory agents in combined regimens is being studied. Interferon, although effective, has little present role in view of the availability of both acyclovir and vidarabine, although it is of interest as a model of an agent that can be administered to outpatients or used in synergistic regimens. The challenge for treatment of CMV is the development of an agent which is effective in vivo. Several promising agents are on the horizon, but much initial work must be done before their effectiveness will become apparent.(ABSTRACT TRUNCATED AT 250 WORDS)