Although different populations of inflammatory cells infiltrate the healing wound, the mechanisms by which they influence the healing process in vivo are poorly defined. In vitro studies suggest that these cells may mediate wound healing by releasing various cytokines within the wound. We measured the levels of interleukin (IL) 1, IL-2, IL-3, IL-4, IL-6, tumor necrosis factor, and macrophage colony-stimulating factor within a subcutaneously implanted polyurethane sponge on various days after injury. Significantly higher levels of IL-1, IL-6, tumor necrosis factor, and macrophage colony-stimulating factor were detected in the wound fluid compared with basal serum levels in nonwounded mice. Tumor necrosis factor, macrophage colony-stimulating factor, and IL-6 peaked earlier than IL-1; however, the levels of these cytokines had fallen by the 13th day after wounding. Interleukin 2, IL-3, and IL-4 could not be detected in the wound fluid, and the wound fluid inhibited the proliferation of the IL-2-dependent cell lines CTLL-2 and HT-2 in response to recombinant IL-2. We hypothesize that tumor necrosis factor, macrophage colony-stimulating factor, IL-1, and IL-6, which are secreted at the site of injury, interact to promote tissue remodeling. The decrease in the levels of these cytokines by the 13th day after wounding may be the result of a regulatory process by the healed wound.