Magnetic resonance (MR) lymphography with superparamagnetic iron oxide (AMI-25) as a contrast agent was developed in an animal model with tumor-bearing lymph nodes. After interstitial administration of 20 mumol of iron per kilogram of body weight into the footpads of rats, the T2 of popliteal and paraaortic lymph nodes decreased from 67 msec +/- 8.2 to 9.5 msec +/- 0.9 and 9.3 msec +/- 0.9, respectively. T2 relaxation times of lymph nodes containing metastases showed a significantly higher value (61 msec +/- 6.2, P less than .005) after interstitial administration of the contrast agent. Intravenous administration of AMI-25 did not produce enhancement of normal or metastatic lymph node relaxation times. The signal intensity of normal lymph nodes decreased profoundly on spin-echo MR images (repetition time of 500 msec, echo time of 30 msec) after interstitial administration, whereas lymph nodes with metastases showed no significant change in signal intensity. Experimental results indicate that MR lymphography may potentially increase the sensitivity of MR imaging the detection of lymphatic malignancy.