Virus particles with the biochemical properties of C-type retroviruses appeared transiently in bone tissues of (C3H x 101) f1 hybrid mice early after treatment with 224 Radium; such particles were then again detected in the bones of the irradiated animals at the onset of osteosarcoma formation and in the osteosarcomas. Antibodies against a murine retrovirus isolated from a 224 Ra-induced osteosarcoma were produced and detected in the serum of the 224 Ra-treated animals within a month after treatment began. The antibody levels plateaued to a maximum after about 2 months and remained elevated until the tumors started to develop. The antibody concentration in the serum of these irradiated animals decreased then progressively to reach levels similar to those observed in untreated controls. It thus appears that the imminence of osteosarcoma development can be predicted by monitoring the anti-C-type virus antibody levels in the serum of the irradiated mice. These experiments also strongly suggest that treatment with 224Radium induces expression of endogenous viruses in the animals.