1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3), has diverse effects in a variety of tissues and cell types, including skin. Since 1,25(OH)(2)D-3 affects both fibroblast and keratinocytes, we evalauated the effect of 1,25(OH)(2)D-3 on wound healing. We investigated the effect of the topically applied 1,25(OH)(2)D-3 or vehicle on the healing of cutaneous wounds in rats in a blinded manner. Wound areas were measured by planimetry technique. Healing was expressed as the percentage of the original wound area that was healed. 1,25(OH)(2)D-3 at concentrations between 5 and 50 ng/day caused a dose-dependent acceleration of healing. Time course and specificity studies indicated that 1,25(OH)(2)D-3 specifically promoted healing between 1-5 days after wounding as compared with vitamin D (0.5 mu g/day), which showed no significant improvement over control. Our results suggest that 1,25(OH)(2)D-3 and its analogues may be anew class of compounds that could be developed to enhance wound healing. (C) 1995 Wiley-Liss, Inc.