Three-hour biodistribution of Tc-99m complexes of six diphosphonates was compared in rabbits with tibial lesions to determine which was best for detection of focal bone lesions. Sr-85 was used as a standard. N,N-dimethylaminomethylene diphosphonate (DMAD) was the only agent with a higher lesion/normal bone ratio than methylene diphosphonate (MDP), attributable to lower concentration in normal bone. Hydroxymethane diphosphonate (HDP) and 2,3-dicarboxypropane-1, 1-diphosphonate (DPD) demonstrated higher concentration than MDP in normal bone without improving lesion contrast. They also exhibited much higher uptake in the liver and kidney, as well as muscle and red marrow in the case of DPD. None was superior to MDP as an all-purpose skeletal agent, though others may be better for specific applications.