Twenty-eight consecutive adult patients with locally advanced (inoperable) or metastatic soft tissue sarcomas were treated with a chemotherapy regimen (CADOM) including cyclophosphamide, ADR, and DTIC on Day 1 of each course, and vincristine with intermediate-dose methotrexate (200 mg/m2) on Day 15 followed by leucovorin rescue. Twenty-four of the patients were evaluable for response and toxicity. Three (13%) achieved a CR after chemotherapy and 6 (25%) a PR. Two of the PRs were converted to CR after surgical removal of residual tumor. All five patients achieving a CR are alive 12 to 30 months after beginning chemotherapy. Median survival of patients achieving a PR was 18 months and of patients achieving an MR was 7 months. Three of five patients with sarcomas arising from the female genitalia achieved a CR. No treatment-related deaths occurred. There were five instances of leukopenia and fever. Nausea and vomiting, and alopecia were common. Stomatitis, muscle cramps, paralytic ileus, and peripheral neuropathy were occasionally observed. The addition of methotrexate did not improve the response rate when compared with our previous CYV ADIC protocol.