In a study of the distribution of 99mTc-polyphosphate and 99mTc-methylene diphosphonate in osteoarthritic femoral heads by macroautoradiography of samples obtained during replacement surgery, the bone-seeking agents were seen to accumulate in the weight-bearing, denuded areas, mainly in the cyst walls and at the osteochondral junctions in the osteophytes. The autoradiographic findings were substantiated by findings from impulse-counting of different zones in the femoral heads that were done on frozen sections. Morphological studies of sections adjacent to the cut surface used for autoradiography showed that the accumulations of the radionuclides were located in areas of new-bone formation, particularly enchondral ossification. This finding was confirmed by histochemical staining for alkaline phosphatase, a marker enzyme for bone mineralization. The over-all distribution of alkaline phosphatase activity in cells roughly paralleled the deposition of the bone-seeking agents. Clinical Relevance: Scintigrams of osteoarthritic joints reflect primarily the rate of osteogenesis in subchondral bone and osteophytes. As the scan is positive even in very early stages in the development of the disease, a more detailed knowledge of the mechanism responsible for an increased uptake of 99mTc-phosphate compounds may, among other things, contribute to the elucidation of the pathogenesis.