The failing human ventricular myocardium undergoes heterogeneous changes at the receptor level that have some impact on the ability of the failing myocardium to respond to inotropic stimuli. In the failing human ventricular myocardium the beta 1-adrenergic receptor is profoundly down-regulated, the beta 2-adrenergic receptor is only slightly decreased, alpha 1-adrenergic receptors are unchanged and VIP receptors appear to be increased in density or affinity. These changes have implications for therapeutic strategies for heart failure and for the natural history and pathogenesis of heart muscle disease.