Ghrelin, a 28 amino acid gastric hormone is a natural ligand of the GH Secretagogue (GHS) receptor (GHS-R) and strongly stimulates GH secretion though, like synthetic GHS, it shows other endocrine and non-endocrine activities. Aim of the present study was to clarify whether ghrelin administration influences insulin and glucose levels in humans. To this goal, we compared the effects of ghrelin, hexarelin, a synthetic GHS, or placebo on insulin and glucose as well as on GH levels in 11 normal young volunteers (age [mean ± SEM]: 28.5 ± 3.1 yr; BMI: 22.2 ± 0.9 Kg/m²). Ghrelin induced very marked increase in GH secretion (ΔAUC^0–180: 5777.1 ± 812.6μ g/l/h; p < 0.01) which was not modified by placebo. Placebo administration did not modify insulin and glucose levels. On the other hand, ghrelin administration induced a prompt increase in glucose levels (ΔAUC^0-180: 1343.1 ± 443.5 mg/dl/h; p < 0.01 vs. saline). Absolute glucose levels at +15′ were already higher than those at baseline (93.9 ± 7.1 mg/dl; p < 0.01) and persisted elevated up to 165′ (90.3 ± 5.8 mg/dl; p < 0.01 vs. 0′). Ghrelin administration was also followed by a decrease in serum insulin levels (ΔAUC^0-180: −207.1 ± 70.5 mU/l/h; p < 0.05 vs. saline). Absolute insulin levels were significantly reduced from 30′ (11.4 ± 0.9 mU/l, p < 0.1 vs. 0′), showed the nadir at +45′ (10.0 ± 0.6 mU/l, p < 0.01 vs. 0′) and then persisted lower (p < 0.01) than baseline up to +105′. Hexarelin administration did not modify glucose and insulin levels despite its marked GH-releasing effect (ΔAUC^0-180: 4156.8 ± 1180.3 μg/l/h; p < 0.01 vs. saline) that was slightly lower (p < 0.05) than that of ghrelin. In conclusion, these findings show that, besides stimulating GH secretion, ghrelin is a gastric hormone possessing metabolic actions such as hyperglycemic effect and lowering effect on insulin secretion in humans, at least after acute administration.