Contraction in cardiac muscle is activated by a combination of Ca influx via sarcolemmal Ca channels and release of Ca from the sarcoplasmic reticulum (SR). The release of Ca from the SR appears to be triggered by Ca influx via a Ca-induced Ca-release mechanism. The amount of Ca influx and Ca released from the SR vary with conditions and with different cardiac muscle preparations. In contrast to the Ca-induced Ca-release process in cardiac muscle, excitation-contraction coupling in skeletal muscle appears to be via a more direct coupling between sarcolemmal voltage sensors and the Ca release (sometimes referred to as depolarization-induced Ca-release). During cardiac relaxation Ca is removed from the cytoplasm by the SR Ca-pump and the sarcolemmal Na/Ca exchange (with the former being somewhat more dominant). Ca extrusion from the cell during both relaxation and diastole is predominantly via Na/Ca exchange, with the sarcolemmal Ca ATPase pump contributing very little. Thus, sarcolemmal Na/Ca exchange appears to be critically involved in the overall regulation of cardiac cellular Ca content.