There are evidences suggesting the involvement of autoimmune mechanisms in the pathogenesis of dilated cardiomyopathy (DCM).Anti-β1/β2-adrenoceptor (AR) autoantibodies have been detected in the sera of some DCM patients which displayed agonist-like effects.Besides, β3-ARs mediate a negative inotropic effect in ventricular cardiomyocytes, which is opposite to that of β1-and β2-ARs.The existence and effects of antiβ3-adrenoceptor autoantibodies (β3-AAs) are unknown.So, the study investigated whether β3-AAs existed in the sera of DCM patients and if so, what may be the biological activities of the autoantibodies? And whether β3-AA can affect the cardiac function? β3-AAs in the sera was screened by ELISA and the biological effects of this autoantibody were evaluated by a motion-edge detection system, intracellular calcium transient detection and patch clamp techniques.β3-AA were administrated to male adult rats with aortic banding surgery.Detect cardiac function, heart/body weight rate and brain natriuretic peptide (BNP) in the sera.The frequency of occurrence and titer of β3-AA in the sera of DCM patients were higher than those in the sera of healthy subjects.Furthermore,the titer of the autoantibodies was positively correlated with ejection fraction of DCM patients.The autoantibody exhibited negative chronotropic and inotropic effects that was accompanied by a decreased intracellular Ca2+ transit and membrane L-type Ca2+ current in cardiomyocytes.β3-AA can decrease the level of BNP in serum and improve the cardiac function of cardiac dysfunction rats.Thus, the presence of β3-AA may inhibit the development and progress of DCM.