Adult progenitor cell transplantation has been proposed for the treatment of heart failure but the mechanisms effecting functional improvements remain unknown. The aim of this study was to test the hypothesis that, in the failing hearts treated with cell transplantation, the mechanical properties and excitation-contraction (EC) coupling of recipient cardiomyocytes are altered. Methods - Adult rats underwent coronary artery ligation, leading to myocardial infarction and chronic heart failure. After three weeks they received intramyocardial injections of either 10⁷ green fluorescence protein (GFP)-positive bone marrow mononuclear cells or 5 x 10⁶ GFP-positive skeletal myoblasts. Four weeks after injection, both cell types increased ejection fraction and reduced cardiomyocyte size. Contractility of isolated GFP-negative cardiomyocytes was monitored by sarcomere shortening assessment, Ca2+ handling by indo-1 and fluo-4 fluorescence and electrophysiology by patch-clamping techniques. Injection of either bone marrow cells or skeletal myoblasts normalized the impaired contractile performance and the prolonged time-to-peak of the Ca²⁺ transient observed in failing cardiomyocytes. The smaller and slower L-type Ca2+ current observed in heart failure normalized after skeletal myoblast, but not bone marrow cell, transplantation. Measurement of Ca2Ca²⁺ sparks suggested a normalization of SR Ca²⁺ leak after skeletal myoblast transplantation. The increased Ca²⁺ wave frequency observed in failing myocytes was reduced by either bone marrow cells or skeletal myoblasts. In conclusion, the morphology, contractile performance and EC coupling of individual recipient cardiomyocytes are altered in failing hearts treated with adult progenitor cell transplantation.