The sarcoplasmic reticulum (SR) of skeletal muscle is an intracellular membranous network that controls the myoplasmic Ca2+ concentration and the contraction-relaxation cycle. Ca2+ release from the terminal cisternae (TC) region of the SR evokes contraction. How electrical depolarization of the transverse tubule is linked to Ca2+ release from the junctionally associated TC is still largely unknown. Independent evidence has been recently obtained indicating that either inositol trisphosphate (IP3) or (and) Ca2+ is (are) the chemical transmitter(s) of excitation-contraction coupling. Here we outline the experimental data in support of each transmitter and discuss possible interactive roles of Ca2+ and IP3.