Radical radiation therapy (5000 rads in 20 fractions in 4 weeks) combined with iv mitomycin (10 mg/m2) and 5-FU (1000 mg/m2/24 hours for 4 days) was used to treat 13 patients with locally advanced but operable squamous cell carcinoma of the anal canal. All patients achieved local control and retained anal continence, and none developed metastases. The patients were followed from 4 to 34 months (median, 12). Severe acute gastrointestinal toxic effects were seen in three patients; the same patients had significant thrombocytopenia or leukopenia. Treatment with this combined program may allow conservative management of squamous cell carcinoma of the anal canal and should be considered as an alternative to abdominoperineal resection.