Fifty patients presenting with first episode genital herpes were randomly allocated to seven day treatment with either oral acyclovir plus 5% acyclovir cream or oral acyclovir plus matching placebo cream. Combined treatment with oral and topical acyclovir was associated with a shorter duration of itching in women alone (p = 0.04) but gave no clinical relief of other symptoms, the time to healing of lesions, or the subsequent recurrence rate. Concomitant topical treatment with 5% acyclovir cream confers no advantages on patients who receive oral acyclovir.