Clinical efficacy and safety of oral acyclovir for the treatment of eczema herpeticum were evaluated in 69 patients in a multicenter, double-blind placebo-controlled trial. Patients were randomly assigned to receive either acyclovir, 200 mg five times per day for five days, or placebo. There were 32 evaluable patients in the acyclovir group and 28 in the placebo group. Clinical efficacy was assessed as very effective, effective, moderately effective, or not effective by using a numerical scoring for various parameters, such as lesion stage, pain, and general improvement. The efficacy rate was 81.3 percent in the acyclovir group and 42.9 percent in the placebo group (p less than 0.01), and significant differences were observed in general improvement and disappearance of ulcer. Results for duration of pain and erosion favored the acyclovir group, but did not reach statistical significance. Mild adverse reactions were documented in two patients receiving acyclovir and in six patients receiving placebo. Oral acyclovir seems to be a well-tolerated and effective therapy for eczema herpeticum.