Of 83 patients with recurrent epidermoid cancer of the anus, 67 had tumors in the anal canal and 16 had tumors at the anal margin. Local pelvic or perineal recurrence after abdominoperineal resection of tumors in the canal had a poor prognosis. Median survival after combination chemotherapy and megavoltage irradiation was 14 months. With irradiation alone, median survival was 7 months, although nearly half of these patients had been treated with orthovoltage techniques. Untreated patients with visceral metastases had a median survival of 8 months, but no improvement in survival was seen after treatment with chemotherapy. In contrast, patients who had metastases in inguinal lymph nodes had a 55% 5-year survival rate after inguinal dissection. Patients with tumors at the anal margin did not have visceral metastases. This is an important difference between tumors arising in the canal and those arising at the anal margin. Local excision was satisfactory treatment for 90% of the patients who had local recurrence in the perianal skin; abdominoperineal resection was rarely required. Inguinal lymph node metastases from margin cancer are uncommon, but three of five such patients survived 5 years after groin dissection. A combination of 5-fluorouracil, mitomycin C, and radiation therapy was used for patients with pelvic recurrence after abdominoperineal resection of epidermoid cancer of the anal canal. In this study, there was no evaluation of the role of megavoltage irradiation alone at the recommended doses of 5500 to 6000 rad for these patients. Some patients with visceral metastases respond to combination chemotherapy, but median survival is not improved; evaluation of new chemotherapeutic regimens is required. Patients with canal tumors metastatic to inguinal nodes should be treated by groin dissection as their prognosis is relatively good. Local recurrence of tumors at the anal margin can be satisfactorily treated by further local excision; those patients with margin tumors metastatic to inguinal nodes require groin dissection.