We studied the interaction between free fatty acids (FFAs) and arginine (ARG) on basal and growth hormone (GH)-releasing hormone (GHRH)-stimulated GH secretion in 14 normal subjects. Compared with placebo, ARG induced a significant increase of GH secretion (334.0 +/- 157.5 v 36.9 +/- 27.6 micrograms/L/h, P < .05). The increased levels of FFAs (1.9 +/- 0.4 mEq/L), obtained by the infusion of a lipid-heparin emulsion, abolished the effect of ARG (55.8 +/- 45.6 v 334.0 +/- 157.5 micrograms/L/h, P < .05). GHRH-induced GH secretion was potentiated by ARG (2,009.9 +/- 463.2 v 922.0 +/- 244.4 micrograms/L/h, P < .05) and suppressed by lipid-heparin infusion (106.2 +/- 28.3 v 922.0 +/- 244.4 micrograms/L/h, P < .01). Moreover, the lipid-heparin infusion inhibited the potentiating effect of ARG on the GHRH-induced GH increase (527.9 +/- 113.6 v 2,009.9 +/- 463.2 micrograms/L/h, P < .01). These results confirm the strong inhibitory effect of FFAs on GH secretion, showing that they are even able to inhibit the potentiating effect of ARG on the GH response to GHRH. Since ARG likely acts via inhibition of hypothalamic somatostatin release, the inhibitory effect of FFAs on GH secretion could take place directly at the pituitary level and/or at the hypothalamic level, counteracting the effect of ARG.