In a prospective randomized study, the chemotherapeutic combination of high-dose methotrexate-citrovorum factor rescue plus cyclophosphamide (MECY) has been shown to be statistically significantly superior to the combination of 5-fluorouracil plus cyclophosphamide (FUCY) in the treatment of Stage III-IV ovarian adenocarcinoma. With MECY, an overall objective remission rate of 67% and a complete remission rate of 48% were achieved. All patients had undergone no treatment except for surgery. In addition to the chemotherapy, patients were randomly allocated to receive or not receive nonspecific immunotherapy with Corynebacterium parvum; this immunotherapy had no apparent effect on the chemotherapeutic response. The study demonstrates a high degree of activity for the MECY regimen, and a comparison between the results with MECY in this study and melphalan in an earlier prospective randomized study provides statistical evidence favoring MECY over single-agent melphalan in the treatment of this disease.