A possible role of the proopiomelanocortin derived peptide gamma 2-melanocyte stimulating hormone (gamma 2-MSH) has been studied in patients with various degrees of congestive heart failure (CHF). The profile of changes in circulating levels of gamma 2-MSH-like immunoreactivity (-LI) has been compared with those of atrial natriuretic peptide (ANP)-LI, arginine vasopressin (AVP)-LI and catecholamines in CHF. Patients with moderate CHF (New York Heart Association stages I-II) showed significantly higher levels of h-alpha ANP-LI and NA (P less than 0.05) compared to controls. Patients with severe CHF (stages III-IV) had significantly higher levels of all hormones measured compared to controls: noradrenaline, P less than 0.001; adrenaline, P less than 0.001; gamma 2-MSH-LI, P less than 0.001; h-alpha ANP-LI, P less than 0.05; AVP-LI, P less than 0.01. For the catecholamines and gamma 2-MSH-LI there was a significant increase from moderate to severe forms of CHF. A significant correlation was observed between gamma 2-MSH-LI and noradrenaline, and between h-alpha ANP-LI and noradrenaline in patients with CHF. The present results show that gamma 2-MSH-LI is increased only in severe forms of cardiac failure, and that this change is more closely related to the increase in circulating levels of noradrenaline than to increased levels of ANP-LI or AVP-LI.