The acute effect of a new GH-releasing peptide, hexarelin (1 mg, iv), on GH secretion and the mechanisms involved in its changes were investigated in conscious sheep. Peripheral GH levels and GH-releasing hormone (GHRH) and somatostatin concentrations in hypophysial portal blood were measured in six rams. An increase in jugular GH levels was observed 15 min after hexarelin injection (9.1 +/- 1.8 vs. 3.9 +/- 0.8 ng/ml; P < 0.05). This was associated with a stimulation of GHRH release into hypophysial portal blood (145.4 +/- 19.9 vs. 59.2 +/- 10.8 pg/ml; P < 0.01) without a change in somatostatin secretion. Our data indicate that GH-releasing peptide-induced GH stimulation in the sheep involves an activation of GHRH neurons in addition to the previously demonstrated direct effect on the pituitary cells.