Green tea polyphenolic catechins exhibit biological activity in a wide variety of cell types. Although reports in the lay and scientific literature suggest therapeutic potential for improving cardiovascular health, the underlying molecular mechanisms of action remain unclear. Previous studies have implicated a wide range of molecular targets in cardiac muscle for the major green tea catechin, (Ϫ)-epigallocatechin-3-gallate (EGCG), but effects were observed only at micromolar concentrations of unclear clinical relevance. Here, we report that nanomolar concentrations of EGCG significantly enhance contractility of intact murine myocytes by increasing electrically evoked Ca 2ϩ transients, sarcoplasmic reticulum (SR) Ca 2ϩ content, and ryanodine receptor type 2 (RyR2) channel open probability. Voltageclamp experiments demonstrate that 10 nM EGCG significantly inhibits the Na ϩ -Ca 2ϩ exchanger. Of importance, other Na ϩ and Ca 2ϩ handling proteins such as Ca 2ϩ -ATPase, Na ϩ -H ϩ exchanger, and Na ϩ -K ϩ -ATPase were not affected by EGCG Յ1 M. Thus, nanomolar EGCG increases contractility in intact myocytes by coordinately modulating SR Ca 2ϩ loading, RyR2-mediated Ca 2ϩ release, and Na ϩ -Ca 2ϩ exchange. Inhibition of Na ϩ -K ϩ -ATPase activity probably contributes to the positive inotropic effects observed at EGCG concentrations Ͼ1 M. These newly recognized actions of nanomolar and micromolar EGCG should be considered when the therapeutic and toxicological potential of green tea supplementation is evaluated and may provide a novel therapeutic strategy for improving contractile function in heart failure.