Cyclic ADP-ribose (cADPR) is the most potent Ca(2+)-mobilizing agent known. It has been found in many different cell types, where it is synthesized from its precursor NAD(+) by ADP-ribosyl cyclases. cADPR binds to Ca(2+) channels in the endoplasmic reticulum membrane to activate a Ca(2+)-release mechanism. This release is itself potentiated by elevated cytoplasmic Ca(2+) concentrations. Thus, cADPR may function as an endogenous regulator of Ca(2+)-induced Ca(2+) release, and there is excitement that it may also function as a Ca(2+)-mobilizing second messenger.