GH secretory profiles in humans are pulsatile and exhibit nocturnal elevation during the early hours of sleep. Fasting augments GH output and rhythmicity. Ghrelin was suggested to exhibit nocturnal increases and to rise in response to nutritional deprivation. We examined whether ghrelin may be an underlying mechanism of GH rhythmicity and response to fasting. We studied nine young healthy subjects during normal feeding and after 2 d of complete fasting. Plasma GH was measured every 10 min, and plasma total and active ghrelins were measured every 20 min. Fasting augmented mean daily plasma GH (1.47 +/- 0.25 vs. 3.30 +/- 0.6 microg/liter; P = 0.012). Neither mean daily total ghrelin (4.19 +/- 0.64 vs. 4.35 +/- 0.74 microg/liter; P = 0.75) nor mean daily active ghrelin (0.13 +/- 0.02 vs. 0.13 +/- 0.02 microg/liter; P = 0.34) changed as a result of fasting. All subjects exhibited nocturnal augmentation of GH secretion; there were no corresponding nocturnal increases in either total or active ghrelin concentrations. Similarly, cross-correlation analysis failed to find any relation between GH and ghrelin pulses. We conclude that ghrelin is unlikely to be of importance in the generation of rhythmic or nutritionally mediated GH secretion.