The human entorhinal cortex (ERC) is an important relay between neocortical association areas and the hippocampus. Pathology in this area, including disturbances in its unique cytoarchitecture and alterations in neurotransmitter receptor binding, has been implicated in several neuropsychiatric disorders but details of the patterns of gene expression for molecules involved in the major neurotransmitter systems in this cortex have been lacking. We used in situ hybridization histochemistry to localize the mRNAs for several proteins which are involved in excitatory and inhibitory neurotransmission in the human ERC. Labelling of mRNA for a glutamate receptor subunit (GluR2) and for a marker of glutamatergic cortical neurons (alpha type II calcium/calmodulin-dependent protein kinase) were distributed in a laminar manner which matched the cellular packing seen on the Nissl sections, with particularly high levels of labelling in the layer II (pre-á) cell clusters characteristic of this cortex. Cells labelled for the mRNA of 67 kDa glutamic acid decarboxylase, the synthesizing enzyme of GABA, were distributed diffusely throughout all layers, not concentrated in the cell clusters, and were present in higher numbers in layer Ill. The labelling of mRNAs for the α1, β2 and γ2 subunits of the GABAA receptor, however, was distributed in a laminar pattern similar to that for GluR2 and CAM II kinase mRNAs, implying a high concentration of inhibitory synapses on the excitatory cells which express these mRNAs.