Voltage-dependent anion channel (VDAC), Bax, and tBid play a central role in apoptosis regulation but their functioning is still very controversial. VDAC forms voltage gated pore in planar lipid bilayers, and acts as the pathway for the movement of substances in and out of the mitochondria by passive diffusion. Here we report that there is increase in the pore size of VDAC in the presence of Bax and tBid through bilayer electrophysiological experiments. We hereby hypothesize that this increase in pore size might cause swelling in the mitochondria, leading to the rupture of mitochondrial outer membrane and release of cytochrome c causing brain cell death. (C) 2004 Elsevier Inc. All rights reserved.