Uptake of bone scanning agents in non-osseous sites has been described in a variety of pathologic conditions including tumor metastases. We have seen several patients in which such uptake was proximal and ipsilateral to the injection site of 99Tcm-methylene diphosphonate, apparently in normal lymph nodes. To further investigate this phenomenon, it was studied in a rat model. Activity in popliteal nodes ipsilateral to the injection site was over 60-fold greater in the animals that received subcutaneous (s.q.) footpad injection compared to femoral IV injection. Ipsilateral popliteal node activity in the s.q. group was 159 times that of contralateral popliteal nodes, with an ipsilateral node to liver ratio of 184:1. In summary, dramatically increased uptake of 99Tcm-MDP in normal lymph nodes ipsilateral and proximal to an extravasated injection has been demonstrated. An awareness of this phenomenon in the clinical setting can avoid confusion with pathologic forms of soft tissue uptake.