Numerous studies have demonstrated evidence of DNA nick end-labeling and DNA laddering following cerebral ischemia. To determine whether genes directly implicated in apoptosis were induced by ischemia, the expression of bcl-2, bcl-x and ICE mRNAs were examined using oligonucleotide probes. Northern blots demonstrated induction of bcl-2 mRNA and bcl-x mRNAs in hippocampus 24 and 72 h following 5 min of global ischemia. In situ hybridization demonstrated induction of bcl-2 and bcl-x mRNAs in CAl pyramidal neurons of hippocampus at 24 h following ischemia which decreased by 72 h. ICE-like mRNA was induced in non-neuronal cells in the CAl region at 72 h following global ischemia. The data show that genes implicated in either protecting against or promoting programmed cell death in other systems are induced following cerebral ischemia. It is hypochesized that CAl neuronal cell death could be accounted for by the failure of the ischemic cells to make protective proteins that protect the cells from an ischemic induced apoptotic-like cell death.