Poor systemic absorption has limited the efficacy of early oral acyclovir in herpes zoster ophthalmicus (HZO). Aqueous humour levels are substantially higher if the drug is administered topically to the eye. A multicentre open randomised study was performed to compare the ocular prophylactic effects of topical and oral acyclovir. Fifty-seven patients with HZO within 72 hours of the onset of rash received either topical acyclovir ointment or 800 mg oral acyclovir, both 5 times daily for 7 days, and were followed for 12 months. Patients receiving ointment were significantly more likely to have ocular complications (p < 0.02) and anterior uveitis was significantly more frequent (p < 0.01) and severe (p < 0.01). Corneal hypoaesthesia was significantly more frequently (p < 0.05) and severe (p < 0.02) at 1 month. From 2 weeks patients receiving ointment were more likely to have pain and at all times their pain was more severe, but these differences were not statistically significant. In spite of its apparently better penetration topical acyclovir appears to have no prophylactic value in the management of early HZO.