The interrelation between the secretion of two hypophysiotropic peptides, growth hormone-releasing factor (GRF) and somatostatin (SRIF), in the generation of episodic growth hormone (GH) secretion was inferred from direct measurements of immunoreactive GRF and immunoreactive SRIF concentrations in the hypophysial-portal plasma of the rat. Secretion of immunoreactive GRF was found to be episodic, with maximal concentrations present during periods of expected GH secretory episodes. Secretion of immunoreactive GRF was accompanied by a moderate reduction in portal plasma levels of immunoreactive SRIF. Passive immunoneutralization of SRIF was associated with increased concentrations of immunoreactive GRF in hypophysial-portal plasma. On the basis of these observations, it appears that each GH secretory episode is initiated by pulsatile secretion of immunoreactive GRF into the portal circulation, which is preceded by or is concurrent with a moderate reduction of inhibitory tone provided by portal immunoreactive SRIF. These experiments provide direct insights into central and adenohypophysial mechanisms by which GRF and SRIF interact to generate episodic secretion of GH.