Long-term observations were made for the development of secondary neoplasms following radiotherapy of animal tumors. Experimental tumors were 3rd generation isotransplants of a mammary carcinoma which arose spontaneously in a C3Hf/He mouse. A single dose of TCD20-TCD98 was followed by weekly observations. Most recurrences were observed in the first 150 days, while only a few were seen in the subsequent 150 days. Secondary neoplasms developed frequently following this period, i.e., 41 out of 67 animals surviving more than 300 days developed secondary neoplasms. They were osteogenic and soft tissue sarcomas, and half the new tumors were found within 490 days after radiotherapy. The results obtained were compared with literature reports of secondary neoplasms following postoperative radiotherapy for carcinoma of the breast and treatment of retinoblastomas. Most of these secondary human neoplasms were nonepithelial sarcomas as in the present study. Secondary carcinomas have been reported following radiotherapy of carcinoma in other locations, i.e., the cervix or head and neck; however, only a limited number of studies have been reported.