A thoretical consideration of the factors which influence the accumulation of radiopharmaceuticals in bone is presented. The avidity with which 99mTc-Sn-pyrophosphate and 18F fluoride are adsorbed by bone crystals has been measured in vitro and the efficiency with which these radiopharmaceuticals are extracted by normal bone has been measured in vivo. It is postulated that alterations in the capillary permeability in the region of a bone lesion greatly influence the target to background ratio that can be obtained with bone seeking radiopharmaceuticals. Quantitiated gamma camera studies in man are presented in support of this hypothesis.