We provide the first evidence for the existence in human plasma of peptides derived from the 66 carboxyl-terminal amino acids of pro-ghrelin (C-ghrelin). C-ghrelin immunoreactivity in plasma was higher than ghrelin, and did not significantly correlate with body mass index in normal health. In patients with myocardial infarction, plasma levels of both ghrelin and C-ghrelin were significantly decreased (similar to30%. P < 0.05), whereas in patients with heart failure, C-ghrelin levels were significantly elevated (similar to32%, P < 0.05) compared with controls. HPLC coupled with RIA showed circulating C-ghrelin to be primarily of low molecular weight (M-r similar to 3500), but in chronic heart failure, a higher molecular weight form (M-r similar to 7500) is also present. This is the first evidence for potential circulating hormones derived from the carboxyl terminus of pro-ghrelin and for their modulation in cardiovascular diseases. (C) 2003 Elsevier Inc. All rights reserved.