Ghrelin stimulates GH secretion, but it is unknown if there is a feedback of GH on ghrelin secretion. In this study, we characterized the relatedness of GH, ghrelin and cortisol in a model of acute caloric deprivation. Ten healthy women (age 26.7±1.6 yrs) were studied during a 4-day fast in the early follicular phase. Q1 hour GH, ghrelin and cortisol were assessed over 24 hours during an isocaloric diet matched to that determined from outpatient food records, and again, after a 4-day complete fast with only water. Sampling during a normal diet at baseline demonstrated that ghrelin decreased 17.9% within 1 hour after meals (P<0.0001), but there was no meal effect on GH. BMI (22.3±0.4 vs. 21.5±0.4 kg/m², P<0.0001) and IGF-I (312±28 vs.124±22 ng/mL, P<0.0001) decreased (baseline vs. day 4 of fasting respectively). Mean 24-hour GH increased (2.6±0.5 vs. 5.6±0.5 ng/mL, P<0.001) but ghrelin decreased (441.3±59.7 vs. 359.8±54.2 pg/mL, P=0.012). The diurnal pattern of ghrelin shifted in response to fasting. The peak ghrelin level decreased from 483.5 pg/mL to 375.6 pg/mL (P<0.0001) and the time of the peak ghrelin changed from 04:15 to 17:15. In contrast, the diurnal pattern of GH was maintained with increases in the nadir (1.1 ng/mL to 3.4 ng/mL) and peak GH concentrations (4.1 ng/mL to 7.9 ng/mL) from the fed to fasted state (P<0.0001). The change in AM GH concentrations was inversely related to the change in ghrelin (r=-0.79, P=0.012). Cortisol demonstrated a diurnal pattern with a significant 60% increase after 4 days of fasting. No relationship was seen between changes in cortisol and ghrelin with fasting. In a second study of a different set of healthy young patients, we examined ghrelin responses to prednisone alone (30 mg PO BID) or prednisone and GH (20µg/kg per day). Ghrelin decreased significantly more in the GH group (309.3 ±20.8 pg/mL to 164.7±12.1 pg/mL) vs. 330.8 pg/mL±45.1 pg/mL to 226.9 ±37.5 pg/mL, P<0.01 for difference between treatment groups by ANCOVA). Most reports demonstrate increased ghrelin among patients with chronic low weight and either no change or increases in ghrelin after overnight and short-term fasting of up to 48 hours, particularly in men. In contrast, we demonstrate that ghrelin decreases with 4-day fasting, even as GH rises, and these processes appear to be reciprocal in healthy women. These data suggest that GH may exhibit feedback inhibition on ghrelin during complete short-term caloric deprivation in healthy women. Our data provide new evidence of the important physiologic relationship of GH and ghrelin in response to changes in protein-energy metabolism.