Twenty-eight patients with squamous cell carcinoma of the anal canal were treated by preoperative radiation therapy and chemotherapy. The radiation therapy was given for 3000 rad (30 Cy) a t 200 rad per day, 5 days a week, to the primary tumor with margin and to the pelvic and inguinal lymph nodes. Chemotherapy was given in the form of 5-fluorouracil infusion 1000 mg/m2 on days 1-4 of the radiation therapy and repeated on days 29-32 of the treatment regimen. Mitomycin C was given in the form of intravenous bolus for 15 mg/m2 on day 1. Surgery was done 4-6 weeks following the last day of radiation treatment. Twelve patients underwent anteroposterior resection, and seven of the 12 had no residual tumor in the surgical specimen, while one patient had microscopic tumor only. An additional 14 patients had complete clinical disappearance of their tumor, and, on excision of the scar, it was found free of microscopic cancer. Two other patients are clinically free of tumor but had no biopsy after therapy. While transient proctitis leukopenia and thrombocytopenia were moderate to severe, no serious complications were observed in these patients. Twenty-two patients are free of tumor and alive one to eight years after treatment. One patient died a cardiac death without tumor four years after surgery. Four patients, all with residual tumor in the specimen, have died of cancer. Their primary lesions were more than 7 cm in maximum diameter a t initial examination. One patient died of disseminated disease with no local recurrence after abdominal perineal resection.