BACKGROUND Transdermal nicotine therapy has shown promise as a smoking cessation aid, but questions about its contact sensitization potential and long-term topical safety have been raised. The purpose of this study was to determine the contact sensitization potential of one nicotine transdermal system (Nicoderm, Marion Merrell Dow Inc, Kansas City, Mo, and ALZA Corporation, Palo Alto, Calif) in a population who were allowed to continue smoking. METHODS This study comprised two phases separated by a 2-week rest interval. During phase 1, a 42-day open-label induction period, subjects wore only active transdermal nicotine systems. During phase 2, a 4-day double-blind challenge period, subjects wore active and placebo systems concurrently. Upon removal of each patch, skin sites were evaluated for signs of irritation, and subjective complaints such as itching or burning were recorded. RESULTS Of the 186 subjects completing the study, 3 (1.6%) exhibited evidence of delayed contact sensitization manifested as erythema with or without infiltration and confined solely to sites of active transdermal nicotine system application. Nonallergic skin irritation was observed in less than 3% of all applications. All reactions resolved without incident. No subjects developed systemic reactions. CONCLUSIONS The transdermal nicotine system used in this trial had a low contact sensitization incidence and was well tolerated topically with minimal irritation.