Progressive epithelial loss (melting) from a previously well-taken graft, healed burn wound, or healed donor site is a significant problem in the treatment of patients with burn injuries. For many years, such epithelial loss was attributed to the growth of Streptococcus spp; however, we recently have encountered progressive epithelial melting without significant colonization or infection with Streptococcus spp. We retrospectively reviewed 1035 cases admitted from January 1994 to July 1996 and then collected data prospectively from 324 patients admitted to the University of Washington Burn Center from August 1996 to May 1997. Melting graft-wound syndrome developed in 29 patients. Swab wound cultures from these patients mainly grew Staphylococcus aureus, and none grew Streptococcus spp. All patients were treated with systemic antibiotics and local wound care. Twenty-seven patients healed spontaneously, but two underwent debridement and re-autografting to close the wounds. The melting graft-wound is a significant clinical problem, and its incidence appears to be increasing. The pathophysiology, clinical course, and treatment of the melting graft-wound syndrome are not well understood, and there is no description of it in the literature. This study describes the clinical features of the syndrome.