We set out to determine whether the central action of growth hormone (GH) secretagogues to induce Fos protein expression in the arcuate nucleus is influenced by central somatostatin action. Conscious male rats were injected i.v. with 100 micrograms sandostatin (octreotide, a long-acting somatostatin analogue) or saline, 10 min before an i.v. injection of either 50 micrograms GH-releasing peptide (GHRP-6), 50 micrograms MK-0677 (a non-peptide GH secretagogue) or saline. In a separate study, conscious male rats were injected i.c.v. with either 2 micrograms sandostatin or artificial cerebrospinal fluid (aCSF) vehicle 20 min before an i.v. injection of 50 micrograms GHRP-6. In all studies, rats were anaesthetized 90 min following GH secretagogue injection, perfused with fixative and the brains processed for the immunocytochemical detection of Fos protein. The number of Fos-positive nuclei detected in the arcuate nucleus of the i.v. sandostatin/i.v. GHRP-6 treated rats (28 +/- 5 nuclei/section) and the i.v. sandostatin/i.v. MK-0677-injected rats (8 +/- 2 nuclei/section) was significantly less than the i.v. saline/i.v. GHRP-6-treated group (56 +/- 5 nuclei/section) and the i.v. saline/ i.v. MK-0677-treated group (20 +/- 2 nuclei/section) respectively. Intracerebroventricular sandostatin injection attenuated the GHRP-6-induced Fos response, from 53 +/- 6 nuclei/section in the i.c.v. aCSF/i.v. GHRP-6 group, to 39 +/- 5 nuclei/section in the i.c.v. sandostatin/i.v. GHRP-6 group. Thus, the central action of GH secretagogues to induce Fos protein expression in the arcuate nucleus appears to be subject to central inhibitory control by somatostatin.