The reported peripheral nerve complications of therapeutic irradiation in humans include brachial and lumbar plexus fibrosis and cranial and peripheral nerve atrophy. We have encountered 9 patients with malignant (7) and atypical (2) peripheral nerve tumors occurring in an irradiated site suggesting that such tumors represent another delayed effect of radiation treatment on peripheral nerve. The neoplasms appeared 4 to 41 years following radio-therapy, at a time when the patients (6 females and 3 males) were 16 to 70 years old and cured of their original tumors. Eight patients had received irradiation to treat malignant disease; the ninth had a benign condition. The sites of peripheral nerve tumor were the brachial plexus in 5, cervical plexus in 1, lumbar plexus in 2, and retroperitoneum in 1. Eight patients presented with painful masses, and in 6 of the 8 there was a progressive neurological deficit. Seven patients died with metastases within two years of diagnosis. In all instances the radio-therapy was within an acceptable radiation dosage, yet 3 patients developed local radiation-induced skin and bony abnormalities. In 3 patients there were either clinical signs or a family history of von Recklinghausen disease, but the malignant peripheral nerve sheath tumors developed only in the radiation port. Animal studies support the clinical observation that malignant peripheral nerve sheath tumors can occur as a delayed effect of irradiation. Other etiological mechanisms, including an increased risk of second primaries in cancer patients and a genetic predisposition to peripheral nerve tumors, may also play a role.