Technetium-99m methylene diphosphonate ([99mTc]MDP) is the most widely used bone-scanning agent today. In order to determine the precise bone locus of 99mTc corresponding to the delayed bone scan image, and to test the potential clinical use of this agent in enhancing the information obtained by bone scan, we employed [99mTc]MDP in this microautoradiographic study of normal bone and bone reparative tissue. Four white rabbits underwent operations in which two 1.5-mm drill holes were created in the subtrochanteric regions of both of their femora. An additional four white rabbits underwent sham operations of their femora, in which neither drilling nor periosteal injury occurred. Two rabbits were controls and did not undergo operation. After 7 days, the first two groups of rabbits were injected with [99mTc]MDP and bone scanned 2 h later. After the scans were completed, all three groups of animals were killed and their femora histologically processed for microautoradiography and routine histopathology. In the two groups that were injected with [99mTc]MDP, all bones showed the isotope to be clearly localized along mineralization fronts. The isotope was occasionally found in the substance of the osteoid, but was absent from the cytoplasm and nuclei of osteoblasts and osteocytes. Osteocytic lacunae showed the presence of isotope at their borders, but no identifiable pattern of isotope uptake was noted. Neither osteoclasts nor Howships lacunae showed isotope uptake.(ABSTRACT TRUNCATED AT 250 WORDS)