Topical tretinoin is highly effective and widely used in the treatment of acne vulgaris. In studies to determine the degree of tretinoin photo degradation (isomerization), 2 tretinoin formulations, tretinoin gel microsphere 0.1% and tretinoin gel 0.025%, alone or in combination with erythromycin-benzoyl peroxide topical gel, were exposed to fluorescent light, incandescent light, or darkness for up to 24 hours. Results of the investigations revealed that after 24 hours of exposure to fluorescent light, 98% of the initial tretinoin in the tretinoin gel microsphere 0.1% formulation remained unchanged. When tretinoin gel microsphere 0.1% was combined with erythromycin-benzoyl peroxide topical gel and exposed to fluorescent light, 99% and 87% of the tretinoin was recovered after 4 and 24 hours, respectively, indicating only a limited amount of degradation. In contrast, exposure of tretinoin gel 0.025% to 24 hours of fluorescent light resulted in up to 69% tretinoin degradation and up to 89% degradation when the gel was combined with the erythromycin-benzoyl peroxide topical gel. The data suggest that the tretinoin gel microsphere 0.1% formulation offers marked protection against tretinoin photo degradation, even in the presence of a strong oxidizing agent such as benzoyl peroxide.