OBJECTIVE. The aim of our study was to evaluate the performance of a new blood-pool contrast agent, MS-325, in depicting regional lymph nodes when injected interstitially and in allowing the subsequent classification of the lymph nodes as normal or tumor-bearing (VX2 tumor). MATERIALS AND METHODS. Six New Zealand white rabbits underwent adapted fast three-dimensional (3D) MR imaging before implantation of VX2 tumor cells in the flank and again 3 weeks after the implantation. For each imaging session, 0.5 mL of undiluted MS-325 was injected subcutaneously into both dorsal foot pads. For more than 120 min, the rabbits underwent repeated 3D MR imaging. The size of the individual lymph nodes and the amount of contrast agent uptake in the nodes were measured 5, 10, 15, 30, 60, and 120 min after the injection. After the rabbits had been sacrificed, their lymph nodes were removed and histopathologically analyzed. RESULTS. In normal as well as tumor-bearing hindlegs, the subcutaneous administration of MS-325 resulted in rapid delineation of popliteal, inguinal, iliac, and paraaortal lymph nodes. Tumor invasion into lymph nodes presented as circumscribed signal voids in the areas infiltrated by tumor, whereas the surrounding residual lymphatic tissue showed enhancement identical to that of normal nodes. CONCLUSION. In addition to providing a safe means of displaying the normal lymphatic system, MS-325-enhanced 3D MR lymphography depicts direct tumor invasion in lymph nodes.