Plasma ghrelin was elevated in chronic heart failure (CHF) patients with cachexia. Obestatin, a sibling of ghrelin, opposes several actions of ghrelin. We, therefore, investigated plasma obestatin and ghrelin levels in patients with CHF. Total plasma ghrelin and obestatin levels were measured in 65 patients with CHF (22 with cardiac cachexia) and 15 controls. Ghrelin levels were significantly higher in patients with cachexia (1237.8+/-47.9 pg/ml) than those without cachexia (P=0.041) and controls (P<0.01). Obestatin levels correlated positively with ghrelin levels, and obestatin levels were significantly increased in patients with cachexia (282.3+/-13.0 pg/ml) than patients without cachexia and controls (both P<0.01). However, the ghrelin to obestatin ratios (4.5+/-0.2) were significantly lower in CHF patients with cachexia than controls (P<0.01). Ghrelin and ratio of ghrelin to obestatin were independent predictors of the development of cardiac cachexia. No association was found between ghrelin, obestatin and New York Heart Association functional class, brain natriuretic peptide. There was disturbance of circulating ghrelin and obestatin in the CHF patients especially those with cachexia, which may have a role in the pathogenesis of cardiac cachexia in CHF.