BACKGROUND/OBJECTIVES The determinants of plasma ghrelin concentrations including the effects of aging, gender, and body composition, are unclear. Appetite and energy intake decrease with advancing age, and there is a corresponding decline in total body lean tissue, and an increase in fat mass. METHODS We measured fasting plasma ghrelin and insulin concentrations in 52 healthy subjects aged 22-82 years, and assessed body composition by dual energy X-ray absorptiometry. Energy intake was estimated from diet diaries. RESULTS Fasting ghrelin concentrations were not significantly correlated with age and energy intake (R = 0.07, P = 0.62; and R = -0.14, P = 0.34 respectively) on univariate regression analysis, and ghrelin concentrations were higher in females than males (2886.8 +/- 182.1 pg/ml vs 2082.5 +/- 121.2 pg/ml; P = 0.001). Ghrelin was inversely related to body mass index (R = -0.328, P = 0.018), fat-free body mass (R = -0.428, P = 0.002), and total skeletal muscle mass (R = -0.439, P = 0.001), but not related to body fat mass (R = 0.177, P = 0.208). On multiple regression analysis, total skeletal muscle mass (corrected for height) was the only significant negative predictor (P < 0.0001) of fasting ghrelin concentrations. CONCLUSIONS In conclusion, in healthy adults, plasma ghrelin concentrations are not significantly influenced by age or energy intake per se, but relate to skeletal muscle mass.