The potential role of the nonconstitutive 72-kDa heat-shock protein (HSP72) in selective neuronal vulnerability to ischemia was studied in rats subjected to graded global ischemia. Immunocytochemistry using a monoclonal antibody against HSP72 was performed on tissue collected after 24 hr of reperfusion. The appearance of HSP72 immunoreactivity correlated in a graded fashion with those regions known to be selectively vulnerable in ischemia. That is, HSP72 was induced in only hilar interneurons and CA1 pyramidal cells following brief ischemia. After intermediate durations of ischemia, HSP72 was expressed in the CA3 neurons and cortical layers 3 and 5, and after the longest intervals, HSP72 appeared in dentate granule cells. Heat-shock protein expression preceded cell death (assessed with acid fuchsin staining) in all regions. This temporal profile suggests that the capability of neurons to express HSP72 is unlikely to account for selective vulnerability of different brain regions following ischemia; its role in neuroprotection during ischemic injury in vivo remains unknown.