A prospective study of patients undergoing major head and neck cancer surgery was undertaken to define the value of preoperative and intraoperative cultures in identifying the patient at "high risk" of wound infection and in predicting the bacteriology of wound infection. One or two days before surgery, the skin of the operative site on the neck, the oropharynx and anterior nares were swabbed. an intraoperative wound culture was obtained after the pharyngeal defect was closed and the wound irrigated with water. All cultures were processed for aerobes in the Anaerobic Bacteriology Research Laboratory at Wadsworth Hospital Center. Wound infections developed in 10 of 31 patients who received cefazolin prophylactically and 21 of 25 patients who received no perioperative antibiotics. Fifty-five percent of infected patients and 68% of noninfected patients demonstrated potential pathogens preoperatively. A potential pathogen isolated preoperatively or intraoperatively was subsequently recovered from 35% of infected wounds. The majority of infected wound cultures grew one or more additional pathogens. A poor correlation was also noted between preoperative nasal Staphylococcus aureus isolation and subsequent recovery from wound infections. We conclude that preoperative and intraoperative aerobic wound cultures are not predictive of the "high risk" patient or of the bacteriology of subsequent wound infection in major head and neck cancer surgery.