The effects of high-dose irradiation on the biomechanical and morphological properties of cortical bone and their time-related changes were studied in male Sprague-Dawley rats. A single fraction of 3500 rads was applied to the middle part of the right thigh. Age and sex-matched control rats that did not receive radiation were used for comparison. Two weeks after irradiation, the animals had lost weight and disappearance of bone cells, shrunken osteocytes, and significantly decreased bone-turnover activities were noted. The bone marrow showed reduced hematopoietic elements and sinusoids with increased fat. No change in the torsional strength and geometric properties of bone was noted at this time. Six to ten weeks after irradiation, histopathological abnormalities of the bone persisted, and there was an accelerated resorption process. However, significant increases in the strength and cortical area of bone appeared only in the non-irradiated, contralateral femur. On the irradiated side, decreased cortical area and increased porosity of bone were found at fourteen to eighteen weeks when compared with the control rats. Other histomorphological properties, such as bone porosity, osteocyte count, and periosteal new-bone formation, appeared to recover eighteen weeks after irradiation, as they became similar to the values for the age-matched normal control rats.