The aim of this study was to determinate whether elevations in circulating free fatty acids (FFA) inhibit in vivo growth hormone (GH) responses to GH-releasing hormone (GHRH) by increasing hypothalamic somatostatin release or by acting directly on the pituitary. Thus, we have studied the effect of an Intralipid-heparin infusion on in vivo GH responses to GHRH in normal rats, normal rats passively immunized with antisomatostatin antiserum, rats with medial hypothalamic ablation, and hypophysectomized rats bearing two hypophyses under the renal capsule. Administration of 1 ml of Intralipid (500 microliters at -30 min and 500 microliters at -25 min) plus heparin (50 IU at -15 min) induced a marked decrease in GH responses to both 1 and 5 micrograms/kg of GHRH (p less than 0.01 at 5, 10 and 15 min for GHRH alone vs. GHRH plus Intralipid). A similar degree of inhibition was obtained after the administration of antisomatostatin antiserum (750 microliters i.v. at -60 min) previous to a challenge with 5 micrograms/kg of GHRH plus 1 ml of Intralipid (p less than 0.05 at 5 and 15 min, and p less than 0.01 at 10 min for GHRH plus normal rabbit serum vs. GHRH plus Intralipid plus antisomatostatin antiserum). Furthermore, administration of 1 ml of Intralipid also markedly reduced GH responses to GHRH in rats with medial hypothalamic ablation (p less than 0.01 at 5, 10, 15 and 30 min for GHRH alone vs. GHRH plus Intralipid) as well as in hypophysectomized rats bearing two hypophyses under the renal capsule (p less than 0.01 at 5, 10 and 15 min for GHRH alone vs. GHRH plus Intralipid).(ABSTRACT TRUNCATED AT 250 WORDS)