Fifty-two patients with locally advanced squamous cell cancer were entered into a randomized trial of BCG vaccine following definitive local therapy. Patients were stratified and randomized to receive BCG vaccine (25 patients) or no adjuvant immunotherapy (27 patients). The BCG vaccine therapy began two weeks following definitive therapy with 2 to 4 X 10(6) Tice strain BCG organisms given intradermally (ID) in alternating sides of the neck every two weeks six times, then every four weeks nine times. In addition, all patients received methotrexate prior to definitive therapy. Median duration of follow-up at the time of analysis was 41 months. Groups were balanced by sex, disease site and stage, histologic grade, and prior therapy. Thirteen (52%) of the BCG vaccine-treated group remain disease free v seven (26%) of the controls. Similarly, 17 (68%) of the BCG vaccine-treated group survived v 11 (41%) of the controls. We conclude regional ID BCG vaccine increases disease-free and actuarial survival in this study population and adjuvant immunotherapy should be further explored in ear, nose, and throat cancer.