Neurotensin, an endogenous peptide and putative neurotransmitter, exhibits a wide range of interactions with dopaminergic neurons and displays some actions akin to neuroleptics. Moreover, neurotensin receptors are abundant in specific layers of the entorhinal cortex where cytoarchitectural abnormalities have been reported in schizophrenia. We therefore examined the entorhinal cortex from postmortem specimens of five control patients and six schizophrenic patients for alterations in neurotensin receptor quantitation and distribution using receptor autoradiography. Specific 125I- neurotensin binding was concentrated in layer II cell clusters, with a 40% reduction in binding in the schizophrenic group (p < 0.05). Moderate binding was observed in both cohorts in deep layers V/VI, with negligible binding in the hippocampus. There was no statistical difference in quantitative neurotensin binding in other lamina of the entorhinal cortex of schizophrenics compared with controls. The characteristic laminar pattern of binding did not differ between cohorts. The reduction in neurotensin binding in schizophrenics is consistent with an increasing number of reports of structural abnormalities in the medial temporal lobe of schizophrenics in general and the entorhinal cortex in particular. Further studies are required to examine the evidence for neuroanatomic and neurochemical pathology in the entorhinal cortex.