Syndecans are a family of four cell surface proteoglycans that bind to various components of the extracellular environment and can regulate many cellular behaviors including growth, adhesion, and movement. To determine whether syndecans can function during wound repair, we have examined expression of the syndecans during wound repair of adult mouse and neonatal or fetal bums skin. Syndecan-1 and -4 were induced in the dermis within 12 h after incisional injury of murine or neonatal human skin. Syndecan-1 was induced primarily on endothelium, and syndecan-4 was present throughout the dermis at the site of injury. Following re-epithelialization, expression of the syndecans return to their, baseline level. In. marked contrast to these observations wounded human fetal skin showed no increase in expression of syndecans. This lack of increase in the expression of syndecans by cells of the dermis correlates with prior observations that fetal skin heals without a polymorphonuclear cell infiltrate, appreciable fibrosis, or clinically apparent scar. Thus, induced expression of syndecans is not an absolute requirement for wound repair but does correlate with the occurrence of fibrosis in mature skin. These findings support the role of syndecans as regulators of cell behavior and suggest that syndecan-1 and -4 induction in the dermis may contribute to events that lead to inflammation and fibrosis.