The effects of GH on the release of somatostatin from the hypothalamus were assessed by measuring the concentrations of immunoreactive somatostatin (IRS) in hypophysial portal blood of urethane-anesthetized male rats. A significant and dose-related increase of IRS in hypophysial portal blood was observed during 20-80 min after a single injection of rat GH (5 and 25 micrograms) into the third ventricle. An intraventricular injection of ovine LH or vehicle alone did not affect IRS values in hypophysial portal blood. When rat GH was repeatedly injected into the cerebral ventricle at 75-min intervals, IRS in hypophysial portal blood rose following each injection in a similar pattern with a latency of 30-45 min. These findings suggest that the release of somatostatin from the hypothalamus is regulated, at least in part, by GH. Furthermore, in view of the inhibitory effect of somatostatin on GH secretion, stimulation by GH of somatostatin release into hypophysial portal blood may be involved in the mechanism by which GH regulates its own secretion.