Viral cultures of mucocutaneous herpes simplex lesions became negative in 5 heart-transplant patients given a 7-day course of intravenous acyclovir. Relief of pain and healing of lesions paralleled the virological response. Similar clinical and virological responses were not seen in the 5 placebo-treated patients in this double-blind placebo-controlled trial. No adverse reactions attributable to acyclovir were noted. Shedding of herpes simplex viruses recurred in 3 patients after acyclovir therapy.