Hepatocyte growth factor (HGF) is a cytokine known to play multiple roles during the various stages of wound healing. This study addresses the ongoing key questions regarding the role of HGF in wound healing, namely: are HGF and its regulators expressed differently in chronic and acute wounds? Biopsies from normal skin (n=10), acute (n=10), and chronic wounds (n=17) were analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction (RT-PCR), and quantitative real-time RT-PCR for the presence of HGF, its receptor cMet, its activators and its inhibitors. Immunohistochemical staining for HGF, HGF activators, and HGF inhibitors was similar, with expression being greater in chronic wound dermis compared with acute wound dermis. While expression of cMet in chronic wound dermis was less than in the acute wound dermis. PCR quantification of these proteins showed similar trends although the differences did not reach statistical significance. The results of this study provide important data confirming the role of HGF in wound healing. In addition, we have demonstrated the aberrant expression of the HGF receptor cMet and activation inhibitors (HAI-1 and HAI-2) in chronic wounds. This aberrant expression may have a value in predicting the process of healing and nonhealing wounds and constitute important targets of future therapies.