BACKGROUND Ghrelin affects the hypothalamic-pituitary-gonadal axis in various nonhuman mammalians, predominantly by suppressing secretion of LH. However, for humans, no such evidence exists. OBJECTIVE Our objective was to study the effect of ghrelin on secretion of LH and testosterone in humans. METHODS Nocturnal (2000-0700 h) secretion profiles of LH and testosterone were determined in 10 healthy males (25.7 +/- 3.0 yr) twice, receiving 50 microg ghrelin or placebo at 2200, 2300, 2400, and 0100 h, in this single-blind, randomized, cross-over study. RESULTS Ghrelin was associated with significantly (P < 0.05) lower mean plasma levels of both LH (2340-0200 h) and testosterone (0040-0300 h) than placebo. LH peak levels of the pulse after first administration of ghrelin/placebo were significantly (P = 0.014) smaller in the ghrelin (2.98 +/- 1.34 mIU/ml) than in the placebo condition (4.37 +/- 1.09 mIU/ml). In addition, the interval between this and the preceding peak was significantly (P = 0.010) longer in the ghrelin (255.8 +/- 79.1 min) than in the placebo condition (190.8 +/- 51.0 min). Significantly (P = 0.005) more LH pulses occurred with placebo (3.2 +/- 0.75) than ghrelin (2.6 +/- 0.7) subsequent to ghrelin/placebo administration. CONCLUSIONS Ghrelin caused both a delay and suppression of the amplitude of LH pulses. These findings are in accordance with those in nonhuman mammalians.