The development of somatostatin analogs with anti-tumor effects has raised hopes for their use in various cancers and tumors of the central nervous system. However, for many therapeutic agents, access to normal brain is retarded by the blood-brain barrier (BBB) and to tumor tissues by a blood-brain tumor barrier (BBTB). We examined the ability of RC-160, a somatostatin analog with known anti-tumor activity, to cross the normal BBB and the BBTB in mice with brain sarcomas. In comparison with the normal BBB, the BBTB was about 10 times more permeable to the vascular marker albumin (radioactively labeled with 99mTc), but the BBTB still represents a substantial barrier. By contrast, the entry rate of RC-160, radioactively labeled with 125I, into brain sarcomas was 60 times higher than into normal brain tissue; more than 1% of the RC-160 injected i.v. was taken up by each gram of brain tumor. These results show that a brain tumor can selectively accumulate the potentially therapeutic agent RC-160.