Application of peritoneal macrophages to experimentally induced cutaneous wounds of old mice accelerates healing to levels almost comparable to those of untreated young animals. Slightly greater acceleration is observed when macrophages are obtained from young as opposed to old donors. These findings are consistent with a defect in macrophage function as a cause of impaired wound healing in senescence and suggest a possible therapeutic strategy.Macrophages play an important role in wound repair (1) and produce substances that stimulate the synthesis of collagen by fibroblasts (2-4). Furthermore, macrophages produce a substance that causes proliferation of fibroblasts in vitro (5). Activated macrophages have been reported to induce vascular proliferation (6). Although attempts were made to characterize the substances produced by macrophages that enhance wound repair, a simpler way to accelerate the healing process was devised. It consisted of mobilizing the macrophages to the wound area and activating them. The effects of topical application of a variety of substances on the repair process of skin wounds in mice were examined. It was found that promotion of wound repair could be achieved in mice by application of glucan (7). The promotion of wound healing by glucan was evaluated later on single animals, by treating an experimental wound on one rear leg (the wound on the other leg serving as a control) in mice, rats, and guinea pigs. Glucan was found to be effective by accelerating the mobilization of macrophages to the wound (7,8). All these experiments were carried out on young animals or on cells in culture.It is generally accepted that cutaneous wounds heal slower in the elderly as compared with the young. This has been confirmed in clinical studies (9-11) and in experimental investigations on mice and rats (12-16, t, §). Wound healing rate has even been used as a biological marker ofage in mice.T Previous results suggested that altered estrogen or androgen levels or altered sensitivity to these steroids could account, at least partially, for the slower wound repair in old rats (16 clipped and shaved on the back. Four cutaneous wounds were made on each animal by lifting the shaved skin perpendicularly to the length of the mouse and punching twice (once anteriorly on the right side and once posteriorly on the left side) with a leather punch (circumference, 4.7 mm), resulting in two wounds on each side. Wounds were photographed immediately and at subsequent times from a fixed distance with the wound surface perpendicular to the axis of the lens. After development of the film, wound images were projected onto paper at a fixed distance, traced with a pencil, and cut out with sharp scissors. The relative sizes ofthe wounds were assessed by weighing the cut-out paper tracings. Healing was assessed from the mean decrease in wound area for the four wounds on each mouse.Preparation and Application of Peritoneal Macrophages. Mice were anesthetized and 0.5 x 1.0-cm oval incisions were made abdominally. A 20-gau...