Using a rapid filtration method, we show that Ag+ is able to trigger Ca2+ release from sarcoplasmic reticulum vesicles at a rate as fast as that induced by Ca2+ itself. The Ag+ concentration dependence of the rate constant of Ca2+ release presents a bell shape, similar to that of Ca2+-induced Ca2+ release, with a maximum at 30 microM free Ag+. The rapid phase of Ca2+-release induced by Ag+ is activated by millimolar ATP and inhibited by 5 microM ruthenium red. Moreover, micromolar Ca2+ produces a shift of the Ag+ concentration dependence of the Ca2+ release rate. All these results suggest that Ag+ acts on the same sites as Ca2+ to regulate the release of Ca2+.