The sodium iodide symporter (NIS) mediates iodide uptake in thyroid cells and enables the effective radioiodide treatment of thyroid cancers. There is much interest in facilitating radioiodide therapy in other cancers by NIS gene transfer. This study showed that exogenous NIS expression decreased MATLyLu rat prostatic adenocarcinoma cell growth. Tumor growth and metastatic progression were significantly delayed in syngeneic rats injected with mixed or clonal populations of MATLyLu-NIS cells compared to rats with control tumors. MATLyLu-NIS tumors in nude mice had a lower, albeit not statistically significant, growth rate than control tumors. The Ki-67 labeling index in NIS-positive areas was lower than in NIS-negative areas of rat tumors derived from a mixed population of MATLyLu-NIS cells. Growth of clonal populations of MATLyLu-NIS cells was delayed in vitro. These results demonstrate that NIS expression inhibits MATLyLu cell growth, thereby providing an additional potential benefit of NIS-mediated gene therapy for cancer.