Experiments have been performed to evaluate the effects of immobilization and of enforced activity on bone growth and development in the young animal and on skeletal mass in the mature animal. Forty growing and 40 adult rats were divided into Groups C and R. Group C underwent cast immobilization of the left hind limb. Group R was subjected to four daily treadmill runs. Animals were given tetracycline, weighed and measured, and sacrificed at 1, 3, and 6 weeks at which time vascular injections were performed. Bones subjected to immobilization and to enforced activity were compared with nonimmobilized control bones by measurements of weight, length and diameter; microradiograms; fluorescence microscopy; microangiograms; and histologic examination. In mature animals, immobilization led to a decrease in bone mass, whereas activity resulted in an increase. In contrast to these data, immobilization in growing animals led to a decrease in whole body weight and length as well as in the length, thickness, and mass of the long bones. Articular surfaces and epiphyseal lines were irregular, bone formation was retarded, and circulation to the femoral head was diminished. Increases in whole body weight and length and in the length, thickness, mass, and epiphyseal circulation of the long bones were observed as results of enforced activity.