Somatostatin (SRIH) receptors are expressed in a large number of neuroendocrine and brain tumors. To evaluate the potential of these tumors locally to produce the SRIH required to bind to SRIH receptors, we have investigated in 158 human tumors whether they express mRNA for SRIH, using in situ hybridization. Among 78 neuroendocrine tumors tested, 13 of 13 medullary thyroid carcinomas, 19 of 34 pheochromocytomas, 3 of 11 paragangliomas, 0 of 4 small cell lung cancers, 4 of 9 adrenal neuroblastomas, and 4 of 7 gastroenteropancreatic tumors contained SRIH mRNA. Among 47 central nervous system and meningeal tumors tested, including 23 meningiomas, 9 astrocytomas, 4 oligodendrogliomas, and 11 glioblastomas, none expressed SRIH mRNA. Unexpectedly, 16 of 33 ovarian tumors, including adenocarcinomas and borderline tumors, expressed SRIH mRNA. These results suggest that a large proportion of neuroendocrine tumors have the ability to express SRIH mRNA, whereas central nervous system tumors do not. The presence of SRIH mRNA in half of the tested ovarian tumors suggests that those tumors may be hormone producing and have neuroendocrine features. The presence of SRIH receptors in most of the neuroendocrine tumors together with the ability of many of those tumors to synthesize SRIH point toward an autocrine regulatory feedback mechanism of SRIH in these tissues.