Background: Adapalene (Differin(R) gel) is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. Objective: We assessed, in healthy volunteers, the skin irritancy potential of three combinations, each including adapalene 0.1% gel and one topical marketed antiacne product. Methods: Twenty-five healthy volunteers were enrolled in a 21-day cumulative irritancy study performed in a double-blind, randomized, controlled intraindividual design. Five days a week, the three materials (benzoyl peroxide, clindamycin phosphate, and erythromycin) were applied in a nonocclusive manner either alone or in combination with adapalene gel on seven cutaneous sites on the upper back Adapalene was applied in the evening whereas the three other materials were applied in the morning. Irritation was evaluated and scored daily except on weekends. Results: All materials were well-tolerated when tested alone. The combinations of adapalene 0.1% gel and either benzoyl peroxide, clindamycin phosphate, or erythromycin were also well-tolerated. The mean cumulative irritancy indices indicated that all three combinations were nonirritating. Conclusion: Under the conditions of the study, all tested treatments alone or in combination appeared nonirritating.