Abstract A clinical study of preoperative irradiation was established as a result of experimental studies which indicated that local recurrence and metastases could essentially be eliminated by administering preoperative irradiation. Using a single 2,000 or 1,500 r dose twenty-four hours before surgery, there was a high incidence of complications. Seventy-nine patients were then studied in a carefully controlled double-blind study using 1,000 r preoperatively. All lesions were squamous cell cancers of the oral pharyngolaryngeal area and were excised by standard but aggressive surgical procedures. The postoperative complications were significantly increased in the patients with irradiation. Although there was a definite trend toward the decrease of local recurrence with preoperative irradiation, there was no statistically significant decrease in the local recurrence rate in the operative wound, nor was there any tendency toward the decrease in incidence of metastases; neither was patient survival prolonged. A carefully controlled and double-blind clinical study gave results which again indicated that tumors in human subjects do not necessarily behave as expected on the basis of studies of experimental tumor systems.