Combined chemotherapy and radiation therapy have been reported to produce a high incidence of complete regression of epithelial cancer of the anal canal, resulting in prolonged disease-free survival. This modality has been advocated as an alternative to abdominoperineal resection as a primary treatment for this disease. Our group treated 19 patients between 1979 and 1985. Treatment included two infusions of 5-fluorouracil (1000 mg/m2/24 hours), one dose of mitomycin C (15 mg/m2), and simultaneous whole-pelvis radiation (3000 rad). The complete response rate was 88%. Three patients had anal cancer incompletely controlled by that therapy. They underwent abdominoperineal resections and are alive without disease at 10, 39, and 43 months, respectively. Actuarial disease-free survival at 40 months was 87.5 +/- 8.8 (% +/- standard error of the mean [SEM]). Complications included gastrointestinal, hematologic, and cutaneous toxicity. These results confirmed a high complete response rate to this therapy. Local treatment failures may occur, but these may be salvaged with abdominoperineal resection.