Forty-seven patients with unresectable desmoid tumors and 32 patients with unresectable fibromatosis were treated with various anti-neoplastic agents including methotrexate, vinblastine, etoposide, actinomycin D, and fluorouracil. A combination of methotrexate with either vinblastine or etoposide was found to be effective in yielding long-term control to both groups of patients. Fluorouracil and actinomycin D were less effective. Other than a significant but slowly reversible peripheral neuropathy in 6 patients, therapy was well tolerated and no long-term hematologic, pulmonary, hepatic, or cardiac toxicity was noted in any patient.