Twenty patients with squamous-cell carcinoma of the anal canal received combined chemo-radiation therapy as their primary treatment. There were 18 women and two men with a mean age of 63 years (range, 34-91 years). The mean follow-up was 34 months (range, 6-62 months). Anal margin cancers and adenocarcinomas were excluded. Fourteen of 20 patients treated had a complete response. There were six local failures: three with residual disease at the end of treatment and three with recurrent disease at a later date. Of the three with residual disease, one underwent abdominoperineal resection and two received salvage therapy (one with chemo-radiation and one with radiation alone). All three patients with recurrent disease were treated with abdominoperineal resection. All six were disease free at the end of the study. Of the 14 patients with complete local response, one presented with liver metastases 19 months later. Sixteen patients (80 percent) were alive at the end of the study, and 19 patients (95 percent) had no evidence of disease. These data add support for salvage therapy in the treatment of patients with residual disease following initial chemo-radiation therapy. Salvage options for patients with squamous-cell carcinoma of the anus who fail the Nigro protocol will be discussed.