Reelin plays a major role in the development of laminated brain structures. In the developing neocortex and hippocampus, Reelin is secreted by Cajal-Retzius cells in the marginal zone. In the present report, we characterize Reelin-immunoreactive neurons in the perinatal and adult human hippocampal formation. Two main populations of cells are described: Cajal-Retzius cells and interneurons. Cajal-Retzius cells are defined as neurons that coexpress Reelin and p73, a nuclear protein of the p53 family. Colocalization experiments of p73 with calcium-binding proteins indicate that most Cajal-Retzius cells express calretinin, but not calbindin. Cajal-Retzius cell density decreases dramatically during the postnatal period, although a few Reelin/p73-positive neurons are still found in the adult. At birth, Reelin-positive, p73-negative neurons are present in all layers of the hippocampal formation. Their morphology and localization indicate that they belong to a heterogeneous population of interneurons. They are numerous in the strata lacunosum-moleculare and radiatum of CA1-CA3, in the hilus, and in the molecular layer of the dentate gyrus, but less common in stratum oriens and alveus, and rare in the principal cell layers. Subpopulations of Reelin-positive interneurons express calretinin or calbindin. The packing density of Reelin-positive cells decreases postnatally, which may be related to the disappearance of Cajal-Retzius cells and to the growth of the hippocampal formation. The presence of Reelin-immunoreactive cells in the adult hippocampal formation indicates that Reelin is not restricted to development but that it may have additional functions in adult life.