In patients undergoing aorto-coronary by-pass surgery, we found a 26 % arterial-venous difference of immunoreactive γ₂-melanocytostimulating hormone (MSH), a proopiomelanocortin (POMC) derived peptide known to possess profound hemodynamic effects. These results prompted an investigation of the presence of γ₂-MSH in the human heart. Using a two-step extraction procedure, regions of human hearts were examined by sensitive and specific radioimmunoassays to determine their γ₂-MSH content. Mean (± SEM) concentrations of 0.14±0.023 pmol/g and 0.12±0.017 were found in right atrium and right ventricle, respectively. High performance liquid chromatography indicated that 80–90 % of the total immunoreactivity eluted in a single sharp peak in a position identical to that of synthetic γ₂-MSH.