We examined the immunohistochemical regional distribution of calcineurin (Ca2+/calmodulin-dependent protein phosphatase) in the adult rat hippocampus, following various regional destruction. In the normal adult rat hippocampus, the calcineurin immunoreactivity showed a characteristic pattern. This protein phosphatase was detected in all layers of the CA1 subfield, including the cytoplasm of the pyramidal cells, whereas it was strongly evident in the stratum lucidum and moderately so in the cytoplasm of pyramidal cells in the CA3 subfield. Seven days after transient forebrain ischemia, which induced destruction of CA1 pyramidal cells, the calcineurin immunoreactivity decreased in all layers of the CA1 subfield, while the immunoreactivity for synapsin I, a marker of the presynaptic site, was preserved. Seven days after the intraventricular injection of kainate, which induced destruction of CA3 pyramidal cells, the calcineurin immunoreactivity in the stratum lucidum was preserved, although the immunostaining pattern of the stratum lucidum changed when CA3 pyramidal cells were destroyed. Seven days after mechanical destruction of the dentate gyrus and CA4 subfield, which induced destruction of mossy fibers, the calcineurin immunoreactivity in the stratum lucidum was lost, except in the far site of the stratum lucidum. In the CA1 subfield, calcineurin was mainly located in postsynaptic sites, while it was mainly located in the presynaptic sites in the mossy fibers of the CA3 subfield. The immunohistochemistry of adjacent sections with antibodies of microtubule-associated protein 2 and synapsin I, which are markers of postsynaptic and presynaptic sites respectively, supports these results. Thus, calcineurin has a different synaptical distribution in the rat hippocampus.