Prior studies have identified two anatomically and neurochemically distinct cellular compartments within the mammalian striatum, termed striosomes and matrix, which express μ-opioid receptors (μOR) and EphA4, respectively. Here we identify and characterize an additional compartment in the rat striatum composed of neurons that express EphA7. In situ hybridization and immunohistochemical data indicate that neurons expressing EphA7 mRNA and protein are arranged in a banded “matrisome-like” pattern confined to the matrix in the dorsal striatum. Within the ventral striatum, EphA7-positive (+) neurons have a less organized mosaic pattern that partially overlaps areas expressing μOR. Immunolabeling data demonstrate that EphA7+ striatofugal axons form distinct fascicles leaving the striatum. Within the globus pallidus, EphA7+ axons terminate primarily within ventromedial areas of the nucleus and along its striatal border. EphA7+ axons avoid regions containing dopamine neurons within the substantia nigra and preferentially innervate areas near the rostral and caudal margins of the nucleus. Within both nuclei, EphA7+ axons have similar but more restricted terminal fields than the entire population of EphA4+ matrix axons, indicating that EphA7+ axons comprise a subpopulation of matrix axons. Ligand binding data demonstrate that ephrin-A5 selectively binds areas of the striatum, globus pallidus, and substantia nigra containing EphA7+ neurons and axons, but not areas expressing only EphA4. Our findings demonstrate that EphA7 expression identifies a novel “matrisome” compartment within the matrix that binds ephrin-A5 and possesses unique axonal projections. Our findings also suggest that EphA7 and ephrin-A5 may participate in the formation of this matrisome subcompartment and its striatofugal projections. J. Comp. Neurol. 521:2663–2679, 2013. © 2013 Wiley Periodicals, Inc.