The neuropeptide somatostatin is the major physiological inhibitor of growth hormone secretion. With the aim of identifying the receptor subtypes through which this neuropeptide may be exerting its neuroendocrine actions in the brain, we have examined by in situ hybridization the distribution of the messenger RNA for SSTR1 and SSTR2 isoforms in the hypothalamus of adult male and female rats. Both receptor subtypes were highly expressed in the medial preoptic area, suprachiasmatic nucleus and arcuate nucleus. High SSTR1, but low SSTR2, expression was evident in the para- and periventricular nuclei as well as in the ventral premammillary nucleus. Conversely, moderate to high SSTR2, but low SSTR1, messenger RNA levels were detected in the anterior hypothalamic nucleus, ventromedial and dorsomedial nuclei and medial tuberal nucleus. Taken together, these distributional patterns conform to those of somatostatin binding sites as visualized by in vitro autoradiography, suggesting that an important proportion of SSTR1 and SSTR2 receptors in the hypothalamus are associated with the perikarya and dendrites of intrinsic neurons. The distribution of SSTR1-expressing cells within the periventricular, paraventricular and suprachiasmatic nuclei was similar to that of neurons previously reported to contain and/or express somatostatin in the brain suggesting that some of the SSTR1 receptors may correspond to autoreceptors. Within the arcuate nucleus, the distribution of SSTR1 and SSTR2 messenger RNA-expressing cells was comparable to that of neurons previously found to selectively bind somatostatin-14 within this area. Given that over one third of these cells also contain and express growth hormone-releasing factor, the present findings suggest that both of these receptor subtypes are involved in the central regulation of growth hormone-releasing factor secretion by somatostatin. Taken together, the present results suggest that SSTR1 and SSTR2 somatostatin receptor messenger RNAs are heavily expressed in those neurons containing somatostatin and/or growth hormone-releasing factor and thereby imply a role for both SSTR1 and SSTR2 somatostatin receptor subtypes in neuroendocrine regulation of growth hormone secretion in both sexes of this species.