Methylene diphosphonate (MDP) was formulated as a complex of 99mTc for skeletal imaging. This agent was compared with three other bone-seeking technetium agents: ethane-1-hydroxy-1, 1-diphosphonate (EHDP), pyrophosphate, and polyphosphate. In tissue radioassay experiments in rodents, the technetium complexes of MDP and EHDP were similar, but skeletal concentration with both of these agents was higher than that with pyrophosphate or polyphosphate. The total-body retention of MDP and EHDP complexed with 95mTc was studied in beagle dogs for 35 days by excretion measurements and total-body counting and compared with polyphosphate and pertechnetate. The long-term retention was greater for MDP. The 5-day cumulative fecal excretion of 95mTc was low when administered as EHDP or polyphosphate complexes and negligible when administered as MDP complex. In six human volunteers the blood clearance of 99mTc-mdp was similar to that of 18F and significantly faster than that of 99mTc-EHDP. Pyrophosphate cleared from the blood much faster than polyphosphate but slower than the diphosphonates. The urinary excretion of the MDP complex was greater than for EHDP within the first 2-3 hr after injection. The 24-hr urinary excretion of pyrophosphate and polyphosphate complexes was not as complete as for the diphosphonates. All four 99mTc complexes proved satisfactory for clinical imaging studies. The MDP complex produced images of superior quality as early as 2 hr after administration, attributable to its more rapid clearance from the blood and soft tissues. On the contrary, a longer interval of 3-4 hr after injection was usually needed for 99mTc-EHDP; pyrophosphate and polyphosphate complexes regularly required a waiting period of 4 hr. Comparitive radiation dose estimates were made based on the available biologic distribution data for these 99mTc skeletal-localizing agents.