Twenty-one patients were enrolled in a randomized, double-blind study that examined the effects of topical 0.05% tretinoin (all-trans-retinoic acid; vitamin A acid; Retin-A) solution on dysplastic nevi. Following histologic confirmation of the diagnosis of dysplastic nevus in three representative lesions, patients applied either tretinoin or a placebo containing 50% alcohol to selected dysplastic nevi once a day under tape occlusion, or twice a day unoccluded, for 4 months. Immediate posttreatment comparative photographs showed marked fading or elimination of some dysplastic nevi clinically, and histologic examination of excisional biopsy specimens showed disappearance or reversion to benign nevi in many of the treated lesions. There were no clinical or histologic changes in those dysplastic nevi treated with placebo. This study shows a definite biological effect of topical tretinoin on some dysplastic nevi.