In a double-blind, placebo-controlled, cross-over trial in 11 patients suffering eight or more episodes of recurrent non-genital herpes simplex virus (HSV) infection per annum, only two patients experienced a recurrence during treatment with oral acyclovir (200 mg 4 times daily) for up to 12 weeks, compared with nine during placebo treatment (P = 0.016). Although lesion development was effectively suppressed in nine of the patients whilst taking acyclovir, the development of prodromal symptoms, and occasionally erythema, was reported by five. There was no difference between acyclovir and placebo in the time to the next recurrence following completion of treatment. No patient reported any side effects of either placebo or acyclovir therapy. It is believed that this is the first report of any form of oral therapy which is effective in suppressing recurrent non-genital HSV infection in immunocompetent patients.