Male A/He mice were given sc injections in the feet with [3,5,3'-125I]triiodothyronine, [125I]T3, either in the free state or encapsulated within sonicated phosphatidylcholine liposomes. Radioactivity was recovered from the injection site, the popliteal lymph nodes (LN), blood, liver, lungs, and spleen at various times (5 min to 6 hr) after injection. The highest level of radioactivity was found in the popliteal LN of mice given liposome-encapsulated (LE) [125I]T3: For more than 3 hours after the injection, radioactivity was fivefold to fiftyfold higher there than that in all the other organs including the popliteal LN of mice given injections of free [125I]T3. The results demonstrated that sc injected liposomes enter the lymphatic pathways and reach the draining LN. Thus local administration of LE antitumor drugs into the sites of a malignant tumor before its excision might be useful in preventing postoperative metastases to the draining LN.