Ghrelin stimulates growth hormone (GH) secretion, but it is unknown whether there is a feedback of GH on ghrelin secretion. In this study, we characterized the relatedness of GH and ghrelin in a model of acute caloric deprivation in 10 healthy women (age 26.7 +/- 1.6 yr) during a 4-day fast in the early follicular phase. GH, ghrelin, and cortisol were assessed every hour over 24 h during an isocaloric diet and after a 4-day complete fast. Sampling during a normal diet at baseline demonstrated that ghrelin decreased 17.9% within 1 h 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 during fasting. Mean 24-h 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 peak ghrelin level decreased from 483.5 to 375.6 pg/ml (P < 0.0001), and the time of the peak ghrelin changed from 0415 to 1715. In contrast, the diurnal pattern of GH was maintained, with increases in the nadir (1.1 to 3.4 ng/ml) and peak GH concentrations (4.1 to 7.9 ng/ml) from the fed to fasted state (P < 0.0001). The change in morning GH concentrations was inversely related to the change in ghrelin (r = -0.79, P = 0.012). During complete short-term caloric deprivation in healthy women, ghrelin decreases, even as GH rises, and these processes appear to be reciprocal, suggesting that GH exhibits feedback inhibition on ghrelin. Our data provide new evidence of the physiological relationship of GH and ghrelin in response to changes in protein-energy metabolism.