Between 1934 and 1983, 23 patients with well-documented diagnosis of radiation-associated sarcoma (RAS) were seen at the University of Michigan Medical Center. The median latent period from irradiation to diagnosis of RAS was 13 years with a minimum latent period of 3 and a maximum of 34 years. All sarcomas originated in previously normal tissues within the irradiated field. Pathology slides available in all patients were reviewed by the same pathologist for the purpose of the study, and the diagnosis of sarcoma was confirmed histologically. There were five bone sarcomas and 18 soft tissue sarcomas. Thirteen patients developed radiation-associated sarcoma following megavoltage treatment with a minimum total radiation dose of 25 Gy in 2 1/2 weeks. The other 10 patients received orthovoltage and/or brachytherapy irradiation alone or combined with external beam radiation. In this group, the radiation doses ranged from 25 Gy to 72 Gy except for one patient who received 8 Gy delivered by orthovoltage irradiation as treatment of knee arthritis. Four patients were originally treated for benign conditions. All the other patients (n = 19) received radiation therapy for a variety of primary malignancies including carcinoma of the cervix (n = 4), brain gliomas (n = 13), Wilm's tumors (n = 2) and retinoblastomas (n = 2), among others.