A perfusion technique was used to study the in vivo effect on bone of parathyroid extract, calcitonin, thyroxine, cortisone, vitamin D3, and acidosis (citric and hydrochloric acids), independent of the reaction of the body, in adult mongrel dogs. The right forelimb was perfused, and the left forelimb served as control site. The material to be studied was mixed with isotonic saline and infused into an artery. All venous return was drained out of the perfused limb through a catheter. Serum calcium, phosphorus, specific gravity, pH, and alkaline phosphatase were determined in arterial and venous blood at intervals during the four-hour perfusion period. The third and fourth metatarsals of both limbs were studied by histological and microradiographic methods. Parathyroid extract increased both bone resorption and bone formation, with hypercalcemia, hyperphosphatemia, and proliferation of osteoclasts. Calcitonin increased bone formation and caused hypocalcemia. Vitamin D3 increased bone formation. Thyroxine enhanced both bone formation and bone resorption, resulting in hypercalcemia and hyperphosphatemia. Citric and hydrochloric acids produced increased levels of serum calcium and phosphorus and decreased pH. However, only citric acid increased bone resorption. There appeared to be no direct effect of cortisone on bone.