The effect of early acyclovir therapy on the course of varicella pneumonia in previously healthy adults was assessed. Medical records from five university-affiliated medical centers were retrospectively reviewed; included were all immunocompetent adults with a clinical diagnosis of primary varicella, a chest radiograph consistent with varicella pneumonia, and an arterial blood gas measurement indicating significant hypoxia. Of the 38 patients who met the study criteria, 11 had had a course of intravenous acyclovir initiated within the first 36 hours of hospitalization; the mean time from admission to initiation of therapy in this early-treatment group was 9.6 hours. The group that received early acyclovir treatment had a lower mean temperature beginning on the fifth day of hospitalization (37.0 degrees C vs. 37.7 degrees C; P = .011) and a lower mean respiratory rate beginning on the sixth day of hospitalization (21 vs. 28 respirations per minute; P = .004). Early acyclovir therapy also resulted in a significant improvement in oxygenation beginning on the sixth day of hospitalization in patients with follow-up arterial blood gas measurements (P = .035). Thus, early institution of acyclovir therapy is associated with reduction in fever and tachypnea and improvement in oxygenation in otherwise healthy adults with varicella pneumonia.