In dogs, osteosarcoma is markedly more frequent in giant breeds than in small ones. Ewing's tumor rarely occurs in species other than man. In children, both osteosarcoma dne Ewing's tumor appear to be related to the rate of bone growth. Nonradiogenic osteosarcoma occurs excessively in persons with the heritable form of retinoblastoma, and in certain malformation syndromes, some of which are known to be genetically induced. Osteosarcoma may also be of the heritable type when it is multicentric or aggregates in families. The neoplasm may occur excessively in certain families with specific cancers not involving bone. By contrast, the only evidence of a genetic influence on Ewing's tumor is its near-absence among blacks in the United States and in Africa. The only exogenous agent known to induce osteosarcoma (but not Ewing's tumor) in man is ionizing radiation in substantial doses. There is no epidemiologic evidence for the virus etiology of bone cancer in man. Despite the epidemiologic differences between osteosarcoma and Ewing's tumor, both histologic types occasionally occur in different portions of the same neoplasm.