A known risk of radiation therapy is the induction of secondary neoplasms, most commonly osteosarcoma and fibrosarcoma. A recent addition to the list of postirradiation neoplasms is neurofibrosarcoma, a Schwann cell or fibroblastic malignancy arising in peripheral nerves, often associated with von Recklinghausen's disease. In a clinicopathologic review of 109 patients with neurofibrosarcoma seen at the Mayo Clinic from 1912 to 1981, the tumors in 12 cases were found to originate in areas that had previously been irradiated for benign or malignant disease. Seven of the 12 patients demonstrated stigmata of von Recklinghausen's disease. The mean latency period between irradiation and clinical presentation of the sarcoma was 15.6 years (range, 5-26 years). Eight patients experienced at least one recurrence; metastases were present in two, and nine patients died of their disease. The mean interval between initial diagnosis and death was 3.4 years. In summary, neurofibrosarcoma may arise secondary to radiation; animal studies on the effects of radiation on peripheral nerves support this concept. It is the authors' opinion that patients with von Recklinghausen's disease should not be unnecessarily irradiated, and that those who do receive radiation therapy should be carefully observed for the development of secondary neurofibrosarcoma.