We have been investigating the therapeutic efficacy of the thymidine analog 5-iodo-2'-deoxyuridine (IUdR) when radiolabeled with the Auger electron emitter 125I in rats bearing intrathecal (i.t.) or intracerebral (i.c.) 9L gliosarcoma solid tumors. [125I]IUdR was infused i.t. (via subarachnoid catheters) or intracerebrally over a 5- or 2-day period; equimolar concentrations of [127I]IUdR were infused into control animals. Hind-leg paralysis and/or survival were followed over time. The results indicate that compared with [127I]IUdR, rats bearing intrathecal tumors and infused i.t. with [125I]IUdR showed significant prolongation of the onset of median paralysis (15.2 versus 9 days). Similarly, the median survival of rats bearing intracerebral tumors and infused i.c. with [125I]IUdR was significantly increased (24 versus 17 days). The data substantiate the antineoplastic potential of [125I]IUdR and indicate a promising role for this radiopharmaceutical in the treatment of CNS cancers.