Two courses of preoperative chemotherapy (methotrexate, bleomycin, cisplatin) were combined with split-course irradiation (2,000 rad/10 preop., 4,000 rad/20 postop.) and prospectively compared with standard therapy (surgery and/or irradiation alone) for locally advanced or recurrent oral/pharyngeal squamous cancer. The chemoradiotherapy arm (Ch-XRT) had 31 patients; the standard therapy arm 28 randomized (RC) and 20 concomitantly-treated (CC) patients. Treatment-related mortality was 17% for Ch-XRT; 10% for RC + CC. Number of patients NED at completion of treatment was 74% for Ch-XRT; 83% for RC + CC (NS). Median survival, however, was 17 months for Ch-XRT, 9 months for CC, and 12 months for RC. In addition, survival at 40 + months was 45% for Ch-XRT versus 21-22% for RC and CC (p less than 0.05). Thus, Ch-XRT seems to have promise in advanced oral/pharyngeal cancer, but needs revision to decrease toxicity.