In this randomized double-blind and placebo controlled trial of 6 months' prophylaxis with acyclovir (ACV) in 42 bone marrow transplant (BMT) recipients, patients receiving ACV had fewer herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections during the prophylaxis compared to the placebo treated patients (P less than 0.05). During the first 6 months after the prophylaxis had been discontinued the frequency of clinical HSV reactivations was low both in the ACV (1/13) and in the placebo (1/13) treated patient groups. Altogether the ACV treated patients had significantly fewer HSV reactivations during the first year after BMT (P less than 0.05). The HSV-specific lymphocyte proliferation response was also lower in the ACV treated group at 3, 6 and 12 months after BMT (P less than 0.05). VZV infections recurred rather frequently, however, after discontinuation of ACV prophylaxis. Therefore no difference was found in the number of VZV infections during the first year after BMT. The VZV-specific lymphocyte proliferation response was significantly lower in the ACV treated group only at 6 months (P less than 0.05). ACV prophylaxis had no effect on the frequency of CMV infections; CMV-specific lymphocyte proliferative responses were not decreased.