Lymph node size, the accumulation of a nodal lymphotrophic contrast agent (LCDIO), and MRI were compared as methods for detecting nodal metastases in an experimental murine model. Lymph node metastases (B16-F1 melanoma expressing green fluorescent protein (GFP) and C57BL/6 mice) were generated to obtain a wide spectrum of nodes, including normal nodes and nodes bearing micrometastases, small metastases, or large metastases. Nodal uptake of LCDIO was measured using 111Indium-labeled LCDIO and was found to be lower in micrometastastic nodes (4.20 ± 1.4%ID/gm) than in normal nodes (8.60 ± 0.22% ID dose/gram, P < 0.005). Nodal tumor burden was quantified from the amount of GFP present in nodes measured using the Western blot method, and was found to correlate with the decrease of LCDIO uptake. By MRI, nodes bearing small and large metastases contained regions of high signal intensity (SI) that corresponded to the visual pattern of tumor in nodes. Micrometastatic nodes were distinguishable from normal nodes based on a diffuse pattern of inhomogeneous SI. The signal-to-background ratio (SBR) of normal nodes (0.0112 ± 0.0061) was different from micrometastatic nodes (0.179 ± 0.080, P < 0.00046) and nodes bearing small metastases (0.723 ± 0.269, P < 0.00013), with high degrees of significance. Magn Reson Med 47:292–297, 2002. © 2002 Wiley-Liss, Inc.