A variety of voltage-gated ion channels are expressed on principal cell dendrites and have been proposed to play a pivotal role in the regulation of dendritic excitability. Previous studies at the light microscopic level demonstrated that the K+ channel subunit Kv2.1 expression was polarized to the cell soma and dendrites of principal neurons throughout the central nervous system. Here, using double immunostaining we now show that Kv2.1 protein is similarly expressed in the majority of cortical and hippocampal parvalbumin, calbindin and somatostatin-containing inhibitory interneurons. At the electron microscopic level Kv2.1 immunoreactivity was primarily observed on the plasma membrane of the somata and proximal dendrites of both principal neurons and inhibitory interneurons; expression was low on smaller dendritic branches, and absent on axons and presynaptic terminals. Kv2.1 subunit expression was highly concentrated on the cell surface membrane immediately facing astrocytic processes. Kv2.1 expression was also concentrated in specific cytoplasmic compartments and on the subsurface cisterns underlying the plasma membrane facing astrocytes. In addition, Kv2.1 subunit immunoreactivity was associated with postsynaptic densities of a fraction of inhibitory symmetric synapses; while expression at asymmetric synapses was rare. These data demonstrate that channels formed by Kv2.1 subunits are uniquely positioned on the soma and principal dendrites of both pyramidal cells and inhibitory interneurons at sites immediately adjacent to astrocytic processes. This close apposition to astrocytes will ensure a rapid removal and limit the influence of K+ released into the extracellular space. This expression pattern suggests that channels formed by Kv2.1 are poised to provide a role in the regulation of neuronal dendritic excitability.