Fifty-three patients with first episodes and 60 patients with prior culture proven recurrent genital herpes were enrolled in a single centre, double-blind, placebo-controlled trial of 5% acyclovir in an aqueous cream base versus matching placebo. For first episodes treated with topical acyclovir the median duration of pain (4 vs. 8 days, P less than 0.05), time to healing of all lesions (8 vs. 14 days, P less than 0.001), duration of viral shedding (4 vs. 11 days, P = 0.001) and duration of new lesion formation (0 vs. 2.5 days, P less than 0.001) were reduced compared with placebo recipients. In patients with recurrent episodes who completed the study topical acyclovir significantly reduced the median duration of all symptoms (3 vs. 6 days, P less than 0.001), the time to healing of all lesions (4 vs. 6 days, P less than 0.01), and the formation of new lesions (5 vs. 29%, P less than 0.01) compared with the controls. Greater clinical benefits were demonstrated in females than in males, particularly for first episodes, but the number of males was small. Topical acyclovir cream is well tolerated and an effective treatment for first and recurrent episodes of genital herpes.