Internucleosomal DNA fragmentation, the characteristics feature of programmed cell death, was demonstrated in gerbil hippocampus following 10 min of forebrain ischemia. Quantitative analysis revealed the presence of DNA fragments as early as 12 h after ischemia, reaching a maximum at 48 h. Measurable DNA fragmentation was still present in 3/3 subjects 96 h after the ischemic insult. In situ staining of hippocampus demonstrated pronounced DNA fragmentation that was localized in the CA1 region. The localization of fragmented DNA to the CA1 is consistent with the vulnerability of this layer to ischemic insult, and indicates that DNA fragmentation may be associated with the delayed loss of CA1 neurons in this model of forebrain ischemia.