Despite the lack of virus-specified thymidine kinase activity, human cytomegalovirus may be sensitive to acyclovir in vitro at concentrations between 10 and 25 mg/l. The inhibitory effect of acyclovir can be further increased by the presence of small amounts of human alpha or beta interferon. Twenty-one allogeneic marrow graft recipients with biopsy-proven cytomegalovirus pneumonia were treated with either high doses of acyclovir (eight patients) or the combination of acyclovir and human alpha (leukocyte) interferon (13 patients). Acyclovir doses of 400 to 1200 mg/m2/dose and interferon doses of 2 to 40 X 10(4) units/kg/day were used. There was no consistent effect of treatment on the likelihood or duration of survival, titre of virus in paired lung specimens, or shedding of virus. However, four patients survived and four others had 2-log or greater decreases in the amount of virus in paired lung specimens, suggesting a possible effect on cytomegalovirus strains with increased sensitivity to these agents. Acyclovir treatment of cytomegalovirus infection may be more effective in patients with lesser degrees of immunosuppression, but was not effective in the treatment of marrow transplant patients with cytomegalovirus pneumonia.