The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha(1A), alpha(1B) and alpha(1E), in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. Al three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha(1A), alpha(1B) and alpha(1E) subunits were differentially localized. In general, alpha(1A)-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha(1B) antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha(1E) staining pattern shared features in common with both alpha(1A) and alpha(1B), with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha(1B) and alpha(1E) staining in the CA3 stratum lucidum with calbindin-immunoreactivity suggested that these two calcium channels subunits may be localized presynaptically in messy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.