Proteins, including cytochrome c, can be released from the intermembrane space after opening of the PTP (Marzo et al., 1998b). PTP opening results in matrix swelling, leading to rupture of the outer mitochondrial membrane. The main arguments for the involvement of the PTP in Bax-induced apoptosis are early observations of a decrease in the transmembrane potential, and the finding that cytochrome c release can be inhibited by cyclosporin A, a PTP inhibitor (Halestrap et al., 1997; Narita et al., 1998). However, it now appears clear that, at least in most forms of apoptosis, the mitochondrial structures remain intact. These would sug gest that activation of the PTP is not involved. However, the intracellular ATP con centration has been shown to influence whether a cell dies by apoptosis or necrosis (Nicotera et al., 1998). It is therefore possible that cells starting to die by the apoptotic pathway could switch to necrotic death, thus activating the PTP.