Immunolocalization of 14-3-3 proteins in human brains with infarction was investigated using isoform-specific antibodies. Neurons around acute or subacute ischemic foci exhibited an enhanced immunoreactivity for 14-3-3 proteins either in the cytoplasm (especially for its sigma isoform) or in the nucleus (especially for its beta isoform), and sometimes in both. 14-3-3-like immunoreactivity was evaluated in each neuron, which enabled us to identify into three patterns: intense cytoplasmic staining with or without nuclear staining; a predominant nuclear staining with weak cytoplasmic staining; and an exclusive nuclear staining without cytoplamic staining. Quantification of 1500 neurons in relation to the severity of ischemia estimated by the relative distance from ischemic foci clarified that nuclear immunoreactivity for 14-3-3 proteins was more frequent in neurons near the ischemic core. Although the cytoplasm of astrocytes was similarly positive for the sigma and the epsilon isoform, their nuclei were only immunopositive for the gamma isoform. In the cerebral white matter with ischemia, axonal swelling and some nuclei of oligodendrocytes were positive for the zeta isoform. Isoform-specific translocation of 14-3-3 proteins into nuclei is a cellular reaction to ischemic stress that may be related to survival of neurons and their protection against cell death.