The messenger RNA (mRNA) expression of somatostatin receptors sst(1-5) was studied in human brain by in situ hybridization histochemistry using specific oligonucleotide probes. sst(1) receptor mRNA was mainly found in the outer and intermediate layers of cerebral cortex, hippocampal formation (CA1, dentate gyrus, entorhinal cortex), hypothalamus, substantia nigra, medullary nuclei and dentate nucleus. sst(2) transcripts were present in the deep layers of the cerebral cortex, amygdala, hippocampal formation (CA1, dentate gyrus, subiculum, entorhinal cortex), the granular layer of the cerebellum and pituitary. sst(3) receptor mRNA was localized in the cerebral cortex, hippocampal formation (CA1, dentate gyrus), several medullary nuclei and the granule and possibly Purkinje cell layer of the cerebellum and at very low levels in the pituitary. sst(4) receptor mRNA was absent in the cerebral cortex. Intermediate signals were observed in the dentate gyrus of the hippocampus and several medullary nuclei while an intense expression was found in the granule and Purkinje cell layer of cerebellum. sst(5) transcripts were present in the pituitary and the granule layer of the cerebellum. The present results show that mRNAs of sst(1-4) somatostatin receptors have distinct distribution patterns within the human brain, although there is overlap in several regions. sst(5) receptor mRNA expression appears to be very low and restricted to the cerebellum and pituitary. The distribution pattern observed in the human brain was broadly similar to that reported previously in the rat brain. The high expression levels of at least two somatostatin receptor subtype mRNAs (sst(2) and sst(5)) in the pituitary gland suggest that somatostatin may affect neuroendocrine functions via more than one receptor.