Patients with 6 or more recurrences per year of herpes labialis were entered into a randomized, double-blind, placebo-controlled, crossover study. During the trial, they applied acyclovir cream for 16 weeks and placebo cream for 16 weeks to all previously affected areas 4 times per day, and were subsequently observed for a further 16 weeks with no treatment. Results from the 23 evaluable cases showed that although recurrences did occur whilst on acyclovir treatment, patients suffered from significantly fewer days of disease and significantly fewer attacks of cold sores when compared with placebo.