Seventy-five cases of primary squamous cell carcinoma of the vagina treated at the University of Pennsylvania are reviewed with long-term follow-up presented. These comprised 2.5% of all female genital malignancies treated during 1958 to 1980 inclusive. Patients treated during that time with non-squamous cell cancers have been excluded. Patients are analyzed with regard to stage, therapy, complications, and survival. Sixty-five percent of patients were stage I or II. Five-year survival for the entire group was 45%. Patients treated with radical surgery other than exenteration did well, with 7 of 8 surviving 5 years. Serious treatment complications were mostly related to radiation therapy and primarily involved the bowel and bladder. Three patients died of complications. Recurrence carried a grave prognosis as 30 of 33 patients with recurrence died of disease. Most recurrences were diagnosed within the first year following treatment. Patients with advanced disease were more likely to have distant recurrences. Although radiation therapy is generally the treatment of choice, radical surgery can yield excellent results when used in carefully selected patients. With meticulous attention to radiation dosage and technique it is hoped that treatment morbidity can be reduced. Optimal treatment of advanced disease may require some form of adjuvant systemic therapy.