Since chemotherapy is generally most effective in killing rapidly dividing cells, the rapidly dividing cells of a fresh surgical wound should be in jeopardy when chemotherapy is given in the early postoperative period. Each of the phases of normal wound healing is theoretically at risk from one or another class of chemotherapeutic agents. Immediately following wounding, inflammation and vascular permeability lead to fibrin deposition and polymorphonuclear neutrophil (PMN), monocyte, and platelet influx. Macrophages are attracted by the activated complement system. By the fourth day the proliferative phase begins, and for the next 20 days fibroblasts produce mucopolysaccharides and collagen. Cross-linking of the collagen fibers then continues for several months in the maturation phase. It seems logical to delay antineoplastic agents for 10-14 days unless there are compelling clinical indications (e.g., superior vena cava syndrome) for more urgent treatment. Administration of folinic acid simultaneously with methotrexate normalizes wound healing. Extravasation of chemotherapeutic agents during intravenous administration may result in severe ulceration and sloughing. The nature of the injury is largely related to the nucleic-acid binding characteristics of the agent. Those agents that do not bind to tissue nucleic acid (vincristine, vinblastine, nitrogen mustard, BCNU, 5-FU) generally cause only local damage from the immediate injury. These substances are quickly metabolized or inactivated, and usual patterns of wound healing can be expected. On the other hand, agents that bind the nucleic acid (doxorubicin, dactinomycin, mitomycin C, mithramycin, and daunorubicin) cause not only immediate toxic reaction in the tissues but, unless excised, continuing and progressive tissue damage. Though some authors have reported success with elevation and ice packs, most recommend surgical excision if there is severe pain, any sign of early necrosis, or significant blistering.