99mTc-Hydroxymethylene diphosphonate (HMDP) was compared to 99mTc-methylene diphosphonate (MDP) with respect to image quality, lesion detectability, and the uptake ratios of normal bone to soft tissue (B/S), metastatic bone to soft tissue (M/S) and bone metastases to normal bone (M/B) at 2 and 3 h after injection in the same subjects. Thirty-three patients with bone metastases were examined in six nuclear-medicine departments, with each center using its usual bone-scanning protocol which was identical for both compounds in the same patient. The uptake of 99mTc-HMDP in normal bone (B/S) was significantly higher than that of MDP at 2 and 3 h, but there were no significant differences between the two compounds with regard to the M/S or M/B ratios. The M/B of HMDP at 2 h was not significantly different from that of MDP at 3 h, the latter showing a significantly higher B/S and M/S ratio. All lesions were detected with both compounds, even at 2 h. The image quality was rated as follows (in decreasing order): HMDP (3 h), MDP (3 h), HMDP (2 h), and MDP (2 h). HMDP was shown to be a useful bone-imaging agent, especially when shorter intervals between injection and recording are required.