The Ca"-mobdizing metabolite cychc ADP-rlbose (cADPR) has been shown to release Ca" from ryanodme-sensitive stores m many cells We show that this metabohte at a concentration of I7 PM. but not Its precursor ,&NAD' nor non-cychc ADPR at the same concentration. is active in releasmg Ca" from rabbit skeletal muscle sarcoplasmlc reticulum. The release was not sensltlce to Ruthemum red (1 PM) nor to the ryanodine receptor-specific scorpion toxin &ct/~otus,-I (10 FM