Bcl-2-related proteins are critical regulators of cell survival that are localized to the outer mitochondrial, outer nuclear and endoplasmic reticulum membranes(1-4). Despite their physiological importance, the biochemical function of Bcl-2-related proteins has remained elusive. The three-dimensional structure of Bcl-x(L), an inhibitor of apoptosis, was recently shown to be similar to the structures of the pore-forming domains of bacterial toxins(5). A key feature of these pore-forming domains is the ability to form ion channels in biological membranes(6,7). Here we demonstrate that Bcl-x(L) shares this functional feature. Like the bacterial toxins, Bcl-X(L) can insert into either synthetic lipid vesicles or planar Lipid bilayers and form an ion-conducting channel. This channel is pH-sensitive and becomes cation-selective at physiological pH. The ion-conducting channel(s) formed by Bcl-x(L) display multiple conductance states that have identical ion selectivity. Together, these data suggest that Bcl-x(L) may maintain cell survival by regulating the permeability of the intracellular membranes to which it is distributed.