131I therapy is a widely accepted treatment for differentiated thyroid cancers which can accumulate iodide. We evaluated the efficiency of 131I therapy against tumors which are transfected with the Na+/I- symporter (NIS) gene. We transfected the rat NIS cDNA expression vector into malignantly transformed rat thyroid cells (FRTL-Tc) which do not concentrate iodide. The resultant cell line (Tc-rNIS) accumulated 125I 60-fold in vitro. The FRTL-Tc cells formed solid tumors after injection of cells into subcutaneous tissues of Fischer 344 rats. Tumors formed with Tc-rNIS cells accumulated up to 27.3% of total 125I administered, and concentrated 125I 11 to 27-fold in the tumors. Extracorporeal measurement of radioactivity in the tumors revealed that 125I accumulation peaked at 90 min, and decreased to half levels 6 h after the injections. To investigate the effect of 131I administration on the tumor growth, we injected Na131I 2 and 3 weeks after the transplantation of the cells. The Na131I did not change the tumor volume significantly in either the FRTL-Tc or the Tc-rNIS-induced tumors. The short (6 h) effective half life of 131I in the tumors diminished the radiation dose to the tumor cells. However, this approach may prove beneficial in the treatment of radiosensitive cancers, and could be employed diagnostically.