Activation of glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) by corticosteroids results in nuclear translocation of the receptor-ligand complex. There, the receptors can bind to DNA for transcriptional regulation. Though this cellular mechanism is well established in cell lines, very little is known about the subcellar behaviour of the receptors in the brain and the associated consequences for DNA binding and gene expression. The aim of this study was to examine the translocation patterns of MR and GR in the different subfields of the rat hippocampus in detail by using immunohistochemistry and confocal imaging. Based on studies that have described differences in receptor expression pattern in the hippocampus and affinities for corticosterone, we hypothesize (1) differences in translocation patterns for the different hippocampal subregions and (2) different translocation speed for MR and GR within one area. Here, we present data on the translocation of MR and GR in hippocampal subregions CA1, CA2, CA3 and dentate gyrus after a single high corticosterone pulse. In order to prevent translocation induced by endogenously synthesized corticosterone, adrenalectomised male Sprague-Dawley rats (n=3) were terminally anaesthetised at 0, 30, 60, or 120 min after i.p. 3 mg/kg corticosterone complexed to HBC to increase solubility. Animals were anesthetized using 0.4 l/min isoflurane intra-nasally. Primary antibodies for MR (MR 1D5 1-18, Gomez-Sanchez et al. 2005) and GR (H300, Santa Cruz Biotechnology) were used for immunofluorescence and confocal microscopy to visualize and quantify the subcellular distribution of the receptors. Results indicate (1) large subregion-specific differences in translocation patterns and (2) different behaviours for MR and GR within areas. Indeed, a strong increase in nuclear immunoreactivity for both GR and MR was observed in CA1 (p<0.001 vs. p<0.01) and CA2 (p<0.01 vs NS) after corticosterone administration. Interestingly, in the DG, a markedly increase was only observed for nuclear GR (p<0.05) while nuclear MR did not change after steroid treatment. The results of this study suggest a revision of the view that MR and GR uniformly translocate to the nucleus upon corticosterone administration. Even though the consequences of this differential translocation in the hippocampus on gene expression and function have to be investigated in more detail, the data suggest that for MR mediated effects ligand availability is more of a limiting factor in the CA1 area, while in other hippocampal subfields the MR signal may be modulated primarily by receptor number or posttranslational modifications. The next step is to study these region-specific translocation patterns of MR and GR in a relevant physiological context, like the ultradian release of corticosterone.