In the light of the relatively poor response of squamous-cell carcinoma of the anus to surgery, an alternative method of treatment has been sought. During the past five years, in a series of 19 patients, the first four were treated by a combination of preoperative irradiation, 5-fluorouracil (5-FU) and mitomycin C as radiosensitizers plus surgery. As a result of complete responses at the time of surgery of all these patients, 15 additional patients have been treated by definitive radiotherapy combined with 5-FU and mitomycin C, thereby avoiding abdominoperineal resection. Eighteen patients had local control, and the one treatment failure is discussed. The method of treatment is described, and recommendations are made concerning techniques to be used or to be avoided.