Sixty-four patients with herpes zoster were entered into a randomised double-masked, placebo-controlled trial of 5% acyclovir cream applied five times daily for 5 days. Of these patients, 56 were included in the final analysis (26 acyclovir, 30 placebo). Significant and objective differences in either progression of the rash, severity of acute pain or incidence of post-herpetic neuralgia were not observed. Although significantly more rashes involuted in the acyclovir group, this isolated finding cannot be explained. Twenty-two patients (12 acyclovir, 10 placebo) experienced erythema or desquamation or both during treatment with the cream. The similar incidence of skin reactions in both groups suggests that they were related to the cream base rather than the acyclovir.