The effects of previous exposure to glucose on the insulin, glucagon, growth hormone and blood glucose responses to subsequent stimulation with L-arginine were investigated in normal man. During control conditions (i.e., after 120 min of saline infusion), the i.v. administration of arginine enhanced the release of all three hormones and caused a small and transient rise in blood glucose. When arginine was preceded by i.v. glucose during 0-60 min, followed by a 'rest period' of 60-120 min, the insulin release induced by the amino acid was further enhanced, glucagon and GH release were unaffected and blood glucose depressed below control levels. When arginine was preceded by a small oral glucose load (0.5 g/kg) the initial insulin response to arginine was augmented, the initial glucagon response was slightly but significantly depressed and blood glucose lowered while the growth hormone response was unaffected. CONCLUSIONS (1) a near-physiological intake of glucose increases insulin and depresses glucagon secretion evoked by amino acids resulting in increased glucose disposal; (2) the modifications of the insulin and glucagon responses constitute separate components in the feed-back regulation of glucose homeostasis.