Arginine stimulates growth hormone (GH) secretion, possibly by inhibiting hypothalamic somatostatin (SS) release. Insulin-like growth factor I (IGF-I) inhibits GH secretion via effects at the pituitary and/or hypothalamus. We hypothesized that if the dominant action of IGF-I is to suppress GH release at the level of the pituitary, then the arginine-induced net increase in GH concentration would be unaffected by an IGF-I infusion. Eight healthy young adults (3 women, 5 men) were studied on day 2 of a 47-h fast for 12 h (35h-47h) on 4 occasions. Saline (Sal) or 10 µg/kg/h recombinant human IGF-I was infused iv for 5 h from 37-42 h of the 47-h fast. Arginine (Arg) (30g iv) or Sal was infused over 30 min during the IGF-I or Sal infusion from 40 to 40.5 h of the fast. Subjects received the following combinations of treatments in random order: 1.) Sal + Sal; 2.) Sal + Arg; 3.) IGF-I + Sal; 4.) IGF-I + Arg. Peak GH concentration on the IGF-I + Arg day was ~45 % of that on the Sal + Arg day. The effect of arginine on net GH release was calculated as ([Sal + Arg] - [Sal + Sal]) -([IGF-I + Arg] - [IGF-I + Sal]). There was no significant effect of IGF-I on net arginine-induced GH release over control conditions. These findings suggest that the negative feedback effect of IGF-I on GH secretion is primarily mediated at the pituitary level and/or at the hypothalamus through a mechanism different from the stimulatory effect of arginine.