Topical administration of tretinoin has proved to be effective in treating clinical signs of photodamaged skin. In large-scale, double-blind, placebo-controlled, 6-month trials, 0.05% tretinoin emollient cream (Renova, Retinova) reduced fine wrinkles and skin roughness, and it produced histologic changes such as epidermal thickening, increased granular layer thickness, stratum corneum compaction, and decreased melanin content. Smaller changes were also observed at lower tretinoin concentrations. Continued for another 6 months, 0.05% tretinoin emollient cream produced some additional clinical improvement but the histologic changes observed in the epidermis (with the exception of melanin content) regressed toward baseline, raising questions as to what was responsible for the clinical improvement. After 12 months of treatment, there were additional signs of tissue normalization including deposition of new collagen in the papillary dermis and ultrastructural evidence of dermal reconstruction with improvement in the dermoepidermal junction and correction of keratinocyte degeneration, changes that presumably relate directly to tretinoin's mechanism of action. There was no suggestion of cytologic atypia in these studies or in biopsy specimens obtained after up to 4 years of continued use. Mild to moderate dermatitis was the only common adverse reaction to tretinoin use. Percutaneous tretinoin absorption is low, raising plasma levels by amounts that are negligible compared with the normally low endogenous tretinoin levels. No teratogenic effects have been observed in retrospective studies of topical tretinoin application during the first trimester of pregnancy. Thus, topical tretinoin is safe and effective in the treatment of photodamage. (J Am Acad Dermatol 1997;36:S27-S36.)