Wound infection was studied prospectively in 23 (6.5%) of 354 patients who participated in a series of antibiotic trials during major contaminated head and neck surgical procedures. Polymicrobial infection was identified in 22 (96%) of 23 cases. The most commonly encountered organisms were aerobic bacteria (91%), anaerobes (74%), and fungi (48%). All fungal infections resolved without systemic antifungal therapy. It was, therefore, concluded that the presence of fungus represented colonization. The primary treatment of an infected wound is surgical drainage accompanied by broad-spectrum antibiotic therapy to prevent sepsis. The value of postoperative wound cultures is unclear. The majority of patients who developed wound infection had a variety of organisms that appeared to be unrelated to the prophylactic antibiotic used, as well as to the particular surgery performed.