Twenty primary osteosarcomas of bone and two osteosarcomas metastatic to the lung were examined by electron microscopy. The tumor cells, whether from an area exhibiting chondroid, osteoid or collagenous matrix, showed common abnormalities in configuration and fine structure. The cells tended to be spindle-shaped with centralized nuclei. The nucleus was enlarged, irregular in shape, and frequently lobulated. The choromatin was dense and arranged around the periphery of the nucleus. There was a large prominent, irregularly shaped nucleolus. Smooth membranes were sparse to absent. The rough endoplasmic reticulum was abundant, disorderly, and tended to be markedly dilated in mature cells. The mitochondria were numerous, variable in size and configuration, and were intimately surrounded by rough endoplasmic reticulum. The collagenous matrix was disorganized with the fibers and bundles randomly oriented and arranged. No structures definitely identifiable as virus-particles were seen. However, microstructures resembling unenveloped nucleocapsids of paramyxo- or related viruses were noted. All fine structure abnormalities could be associated with an increased metabolic rate and/or with abnormal protein and enzyme synthesis. No definitive diagnostic features were found. The fine structure of cell cultures derived from the osteosarcomas in this study was similar to that of the fresh tissue. No virus-like particles were seen in any of these cell lines.