A vital characteristic of skin is its ability for wound repair in response to injury. A transient elevation of matrix metalloproteinases (MMP) in the epidermal and dermal compartments of healing wounds implicates the MMP family of enzymes in the regulation of events important to injury repair. Transgenic mice expressing human interstitial collagenase (MMP-1) in the epidermis were used to perturb the regulation of this proteinase in order to examine the role of epidermal collagenase during wound healing. The relative healing potential of collagenase transgenic mice and wild-type littermates was assessed by measurements of the wound area during closure of full-thickness wounds. Transgenic mice exhibited a 2-3 d delay in the time required to reach 50% closure of 6 mm wounds. Histologic analysis of the transgenic wound bed revealed the retarded migration of the epithelium across the open wound. The results are consistent with the hypothesis that control of collagenase (MMP-1) expression is important for re-epithelialization during wound healing and indicate that collagenase regulation is critical to the kinetics of normal wound closure.