Abnormal Ca(2+)-homeostasis is a hall-marked characteristic of the failing heart. In the normal myocardium, the sarcoplasmic reticulum (SR) is a principal organelle that controls intracellular Ca(2+) concentration during the cardiac cycle. The SR consists of longitudinal and terminal cisternea regions. The former contains the Ca(2+)-ATPase pump or SERCA-2a whose function is to transport cytosolic Ca(2+) into the lumen of the SR during diastole and whose activity is regulated by reversible phosphorylation of the endogenously SR-bound phospholamban (PLB). The SR's terminal cisternea region contains ryanodine-sensitive Ca(2+)-release channels (RR), the activity of which is regulated by direct and indirect reversible phosphorylation. These channels release the SR-stored Ca(2+) during contraction. We have shown that in left ventricular (LV) myocardium from dogs with coronary microembolization-induced heart failure, ability of the SR to sequester and release Ca(2+) during the cardiac cycles is impaired. This abnormality was associated with reduced expression (protein and mRNA) levels of Ca(2+)-ATPase, PLB, and reduced PLB phosphorylation. Long-term therapy with the Acorn Cardiac Support Device (CSD) is associated with restoration of the ability of the SR to sequester Ca(2+). This improvement in SR function following chronic CSD therapy was due primarily to increased affinity of the SERCA-2a for calcium. The later was associated with (1) increased phosphorylation of PLB at serine 16 and threonine 17, (2) unchanged protein expression of PLB and (3) unchanged protein expression of SERCA-2a in LV myocardium of CSD-treated dogs compared to controls. This review summarizes our current understanding of the role of the CSD in modulating SR calcium cycling in an experimental canine model of chronic heart failure produced by multiple sequential intracoronary microembolizations.