Bcl-2 can rescue neurons from death and might, therefore, exert its action by associating with neuron-specific proteins. Using LexA-Bcl-2 as bait, we find that the cellular prion protein (PrP) interacts with Bcl-2, but not Bax, in the yeast two-hybrid system. Since the PrP gene has been implicated in neurodegenerative disorders, this preliminary observation suggests a potential pathogenic mechanism for these conditions.