The gut peptide, ghrelin, may participate in the control of energy homeostasis and pituitary hormone secretion in humans, stimulating both food intake and, at pharmacological doses, ACTH and cortisol secretion. Meal consumption and weight loss regulate ghrelin levels, but less is known about the relationship of ghrelin to body composition, aging, menopausal status, and lipid metabolism. Therefore, 60 adult men and women of widely varying ages and weights were characterized in terms of body composition and levels of ghrelin, glucose, insulin, lipids, and cortisol. Fasting ghrelin levels correlated positively with age and negatively with BMI and fat cell size, but were not related to fat mass, intraabdominal fat, or lean mass. Fasting ghrelin levels correlated most strongly with insulin levels (r = -0.39; P = 0.002), insulin resistance as determined by the quantitative insulin sensitivity check index (r = 0.38; P = 0.003), and high-density lipoprotein cholesterol levels (r = 0.33; P = 0.009). Meal-induced ghrelin suppression correlated with the postprandial rise in insulin (r = 0.39; P < 0.05). Ghrelin levels were similar in men and women and did not vary by menopausal status or in association with cortisol levels. Our data are consistent with the hypotheses that insulin may negatively regulate ghrelin and that high-density lipoprotein may be a carrier particle for circulating ghrelin.