A prospective double-blind comparison of 99mTc-hydroxymethane diphosphonate (HMDP) and 99mTc-methylene diphosphonate (MDP) as bone-seeking agents was performed with 102 patients. Densitometry showed that both cancellous/compact bone and cancellous bone/soft-tissue ratios were greater with HMDP (p less than 0.05); compact bone/soft-tissue and bone lesion/normal bone ratios were the same with both agents. Bone delineation, soft-tissue uptake, and overall image quality were the same with both agents. The HMDP formulation contained 78% fewer stannous ions and had a longer useful life after technetium labeling than MDP.