To evaluate the in-vivo and in-vivo stability of methylene diphosphonate (MDP)-Tc-99m, relative ligand exchange rates in phosphate buffer between MDP-Tc-99m and human serum albumin(HSA), and between pyrophosphate (PYP)-Tc-99m and HSA have been measured. Gel permeation chromatography has also been carried out to estimate relative rates of ligand exchange between polysaccharide and the Tc-99m-bone agents. The in-vitro stability was further correlated with its specific radioactivity. The results indicated that the MDP-Tc- 99m is more stable than the PYP-Tc-99m but less stable than MIDA-Tc-99m, HIDA-Tc-99m, and DTPA-Tc-99m etc. in refering to other data. In stability point of view, MDP-Tc-99m is considered to be a better bone agent than PYP-Tc-99m since MDP-Tc-99m can be accumulated at bone by a smooth transfer of Tc-99m to hydroxyapatite, whereas in case of PYP-Tc-99m, most of the Tc-99m is transferred to HSA before arriving to the hydroxyapatite.