Background: Before the September 1996 approval of 1% penciclovir cream for the treatment of herpes labialis, no other prescription topical therapy was approved for the treatment of this recurrent viral disease affecting approximately 20% of the adult population of the United States. Local anesthetics, such as tetracaine, have been used in over-the-counter topical products, but are only labeled for the relief of pain and itching associated with cold sores and fever blisters. Objective: The purpose of this study was to determine whether a topical preparation of a tetracaine cream is safe and effective in the treatment of recurrent herpes labialis in immunocompetent patients. Methods: A double-blind, placebo-controlled study was conducted to assess the relative effectiveness and safety of 1.8% tetracaine equivalent in a cream base versus placebo in the treatment of herpes labialis in immunocompetent adults. In this study, patients applied medication up to 6 times daily until the lesions healed (scab loss), but for no more than 12 days. The patients were monitored on the day of enrollment, once during the course of treatment, and at a final visit after the lesions had healed. Patients assessed themselves the day of scab formation and the day the scab fell off. They also graded, on a daily basis, their perception of relief from itching and pain and the overall benefit. Results: The results from 72 patients (35 = placebo; 37 = active) showed that scab formation occurred in a mean of 2.4 ± 0.27 days for the placebo group and 2.3 ± 0.26 days for the active group. Healing time (scab loss) occurred in a mean 7.2 ± 0.36 days for the placebo group and in 5.1 ± 0.35 days in the active group. The difference observed for healing time between the placebo and the active tetracaine cream was statistically significant (P = .0002). This represents an approximately 30% reduction in the healing time for the active group compared with the placebo group. In addition, the study patients ranked the benefit of their treatment on a daily basis and graded the overall benefit of the therapy at their final visit. The ranking was on a 1 to 10 index scale (1 = no benefit at all; 10 = very effective treatment). At the final visit there was a statistically significant difference in the benefit index for active preparation versus placebo for this subjective evaluation (placebo index, 5.9 ± 0.6; active index, 7.3 ± 0.48 [P = .0359]). The subjects also evaluated relief from itching and pain on a daily basis. Relief from itching was significantly greater in the active group than in the placebo group on days 2 and 3 after initiation of the treatment. Pain was not found to be severe in either the placebo or active treatment groups. At day 2 of treatment and beyond, pain scores never were greater than 3.2 ± 0.28 for active on a scale in which 1.0 represented “no pain at all” and 10 represented “most severe pain imaginable.” Although mean values for pain were always less for the active therapy, lesional pain scores never reached statistically significant lower values for active compared with placebo. Conclusion: Our findings indicate that a 1.8% topical tetracaine cream, when applied frequently, significantly reduces the healing time of recurrent herpes labialis lesions. Additionally, it is perceived by the study subjects to reduce itching of the lesions and to have a beneficial overall effect. (J Am Acad Dermatol 1999;41:996-1001.)