Pretreatment of skin with all-trans retinoic acid (tretinoin) has been shown to enhance wound healing. Previous studies have mainly used animal models to demonstrate this effect. We wanted to determine whether pretreatment could promote wound healing in severely photoaged dorsal forearm skin. Four elderly men with severely actinically damaged forearms were treated daily for 16 weeks. One arm was treated with 0.05-0.1% tretinoin cream (Retin A, Ortho), and the other with Purpose cream (Ortho) as a vehicle control. Four-millimetre punch biopsies were taken from both dorsal forearms prior to treatment. After 16 weeks, full-thickness 2-mm punch biopsies were taken from both sides. Serial photographs were taken, and healing of the wounds quantitatively assessed by image analysis. On the 11th day, the wounds were excised using a 4-mm biopsy punch. Biopsies were processed for light microscopy. After 16 weeks, the tretinoin-treated forearms showed moderate erythema and scaling. Polarized light photographs revealed multiple, red, vascularized foci and/or a diffuse network of small vessels. The histological effects were typical for tretinoin, i.e. compaction of the stratum corneum, epidermal acanthosis with correction of atypia, an increase in small vessels, and increased cellularity in the upper dermis. Purpose cream had no effect, either clinically or histologically. On the tretinoin-treated side, the wound areas were 35-37% smaller on days 1 and 4, and 47-50% smaller on days 6, 8, 11, compared with the controls. Clinically and histologically, reepithelialization occurred more rapidly. Thus tretinoin dramatically accelerated wound healing in photodamaged skin.