OBJECTIVE We wished to investigate the interaction of arginine, GHRH and insulin stress on GH secretion. DESIGN Six healthy, non-obese volunteers underwent seven separate studies in random order. They received (1) insulin alone al 0 minutes; (2) GHRH alone at 15 minutes; (3) arginine alone at 0-30 minutes; (4) arginine at 0-30 minutes and GHRH at 15 minutes; (5) insulin at 0 minutes and arginine at 0-30 minutes; (6) insulin al 0 minutes, GHRH at 15 minutes and arginine at 0-30 minutes; (7) insulin at 0 minutes and GHRH at 15 minutes. MEASUREMENTS GH and PRL were measured from - 30 to 150 minutes at intervals of 15 minutes. RESULTS Arginine increased GH responses to GHRH and decreased GH responses to hypoglycaemia, but this inhibitory effect of arginine was reversed by GHRH. CONCLUSIONS The findings suggest that arginine-induced GH release is mainly mediated by a decrease in somatostatinergic tone, while GH responses to insulin stress are probably mediated by both an increase in hypothalamic GHRH release and inhibition of somatostatin.