In a 16-week randomized, double-blind, vehicle-controlled study of topical tretinoin in the treatment of photoaging, all patients applied topical tretinoin to one forearm and vehicle cream to the other. Half of the patients received tretinoin to the face, and half received vehicle cream. All 30 patients who completed the study showed statistically significant improvement in photoaging on the tretinoin-treated forearms, but not on the vehicle-treated forearms. Fourteen of the 15 patients who received tretinoin to the face had improvement in photoaging, whereas none of the vehicle-treated patients' faces improved, a statistically significant difference in response between the two groups. Statistically significant histologic changes were seen in forearm skin treated with tretinoin, but not with vehicle cream. Side effects were limited to irritation of tretinoin-exposed skin.