The Wnt family of developmental genes has previously been shown to be involved in proliferation, differentiation, and cell to cell signaling during embryogenesis. In addition, several Wnt genes have been shown to be expressed during carcinogenesis. We have investigated these genes during the wound-healing process. Wnt-4 gene expression is found in mouse wounds from 2 hours to 30 hours postwounding. The expression of Wnt-4 is also stimulated by direct trauma to murine fibroblasts in culture, and the expression is greatly enhanced by the addition of a short plasmin digest of fibrin. Therefore the regulation of Wnt-4, appears to be complex, with expression being stimulated both by direct trauma and by the influence of clotting and fibrinolysis products. We propose that the expression of Wnt-4 in the early wound, in response to the provisional fibrin matrix, regulates cell movement and proliferation in the creation of new tissue by mechanisms related to those of embryogenesis.