Sixty adult male rats were used to study the effect of the anti-inflammatory drug Ibuprofen on fracture callus and perpendicular skeleton. After experimental periods of 3 and 9 weeks, fracture callus and both fractured and unfractured tibiae were examined with respect to bone mass and composition and45Ca metabolism. No significant changes were found in the composition of fracture callus during treatment. Significantly diminished parameters of both fractured and unfractured tibia were observed for wet and dry weights, ash content, and organic matter after 3 weeks but the bone mass had become almost restored and the changes were non-significant during treatment 9 weeks following fracturing. The45Ca activity was elevated significantly in fracture callus and fractured tibia 3 weeks after fracturing but had definitely declined to physiological levels at 9 weeks. Serum45Ca activity was significantly elevated during Ibuprofen treatment. The findings support the concept that Ibuprofen lessens the bone mass and composition of both fractured and unfractured tibia and also activates the calcium metabolism in fracture callus. In the long run, however, this effect is weakened and the bone changes are become almost normal. Some explanations regarding these short-term effects of Ibuprofen are discussed.