The treatment of brain malignancies with boron neutron capture therapy depends on their ability to cross the blood-brain barrier (BBB). An especially promising class of boron-containing compounds is the rhenacarboranes that, if able to cross the BBB, could act as delivery vehicles as well as a source of boron. Here, we examined the ability of the 3-NO-3,3-kappa(2)-(2,2'-N(2)C(10)H(6)(Me)[(CH(2))(7)(131)I]-4,4')-closo-3,1,2-ReC(2)B(9)H(11) (rhenacarborane) labeled with iodine-131 to be taken up into the bloodstream after subcutaneous administration and to cross the BBB. The (131)I-rhenacarborane was quickly absorbed from the injection site and reached a steady state in arterial serum of 2.59%/ml of the administered dose. Between 73 and 95% of the radioactivity in serum 6 h after administration represented intact (131)I-rhenacarborane. Its octanol/buffer partition coefficient was 1.74, showing it to be lipophilic. Tissue/serum ratios for brain, lung, and liver showed classic patterns for a lipid-soluble substance with high levels immediately achieved and rapid redistribution. For brain, a steady state of approximately 0.107% of the administered dose/gram-brain was rapidly reached, and 71% of the radioactivity in brain 6 h after subcutaneous administration represented intact (131)I-rhenacarborane. Steady-state values were 1.53 and 0.89% of the injected dose per gram for lung and liver, respectively. (131)I-Rhenacarborane was quickly effluxed from brain by a nonsaturable system after its injection into the lateral ventricle of the brain. In conclusion, these results show that a rhenacarborane was enzymatically resistant and able to cross the BBB by transmembrane diffusion and accumulate in brain in substantial amounts. This supports their use as therapeutic agents for targeting the central nervous system.