Proteins of the Bcl-2 family are intracellular membrane-associated proteins that regulate programmed cell death (apoptosis) either positively or negatively by as yet unknown mechanisms. Bar, a pro-apoptotic member of the Bcl-2 family, was shown to form channels in lipid membranes. Bar triggered the release of liposome-encapsulated carboxyfluorescein at both neutral and acidic pH. AS physiological pH, release could be blocked by Bcl-2, Bcl-2, in contrast, triggered carboxyfluorescein release at acidic pH only. In planar lipid bilayers, Bar formed pH- and voltage-dependent ion-conducting channels. Thus, the pro-apoptotic effects of Bar may be elicited through an intrinsic pore-forming activity that can be antagonized by Bcl-2.