Here we present the determination of the three-dimensional structure of the skeletal muscle Ca2+-release channel in an open state using electron cryomicroscopy and angular reconstitution. In contrast to our reconstruction of the channel in its closed state, the density map of the channel driven towards its open state, by the presence of Ca2+ and ryanodine, features a central opening in the transmembrane region-the likely passageway for Ca2+ ions from the sarcoplasmic reticulum to the cytosol. The opening of the channel is associated with a 4 degree rotation of its transmembrane region with respect to its cytoplasmic region, and with significant mass translocations within the entire cytoplasmic region of the channel tetramer.