&NA;Thirty patients with epidermoid carcinoma of the anus, ranging in age from 40 to 89 years, were treated with combined chemotherapy (CT) and radiation therapy (RT) in lieu of abdominoperineal resection. Two courses of 5‐FU (1000 mg/m2/day×four days) by continuous infusion and mitomycin‐C (10‐15 mg/m2IV bolus on day 1 of each course) were given 3 to 4 weeks apart simultaneously, with whole pelvis RT to 4140 to 4500 cGy. Twenty‐one of 28 patients had T3‐T4primaries and ten had positive nodes (N1). Two of the 30 patients were treated for local recurrence following surgical excision and one was treated immediately after local excision. Twenty‐six of the 30 patients attained biopsy‐confirmed complete remission. Four of the 30 patients demonstrated residual disease at completion of therapy but all subsequently achieved complete remission with additional nonsurgical treatment. One patient, initially treated for local recurrence following excision failed locally at four years and was salvaged with chemotherapy followed by abdominoperineal resection. No patient has experienced distant failure. Twenty‐seven of 30 patients were alive and disease free after 9 to 76 months of follow‐up and three died, disease‐free, of unrelated causes. Acute toxicities were mild and did not necessitate interruption of treatment. A brisk perineal reaction and diarrhea were noted in all patients. Late complications were unusual. All patients were treated in a community‐based, private practice setting. The authors conclude that combined CT‐RT, as employed herein, represents a first‐line curative treatment for the majority of patients with epidermoid anal carcinoma. For patients who demonstrate residual disease following this therapy, salvage regimens such as 5‐FU infusion and cisplatin, or sequential MTX‐5‐FU‐Leucovorin with additional synchronous RT should be employed before resorting to radical surgery.