IMPORTANCE: Alterations in glutamatergic neurotransmission have been postulated to be a key pathophysiologic mechanism in schizophrenia. OBJECTIVE: To evaluate hippocampal volumetric measures and neurometabolites in unmedicated patients with schizophrenia and the correlations between these markers. Our a priori hypothesis was that glutamate levels would negatively correlate with hippocampal volume in schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Combined 3-T structural magnetic resonance imaging and single-voxel proton magnetic resonance spectroscopy study at the Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, of 27 unmedicated patients with schizophrenia and 27 healthy controls. MAIN OUTCOMES AND MEASURES: Hippocampal volumetric measures and neurometabolites, and the correlations between volumetric measurements and neurometabolites. RESULTS: Hippocampal volumetric deficits, increased ratios of hippocampal glutamate and glutamine to creatine (Glx/Cr), and a loss of correlation between hippocampal N-acetylaspartate (NAA)/Cr and Glx/Cr in patients with schizophrenia were found. Significant correlations between hippocampal volumetric measures and Glx/Cr were also found in patients with schizophrenia but not healthy controls. CONCLUSIONS AND RELEVANCE: Our findings support the theory that alterations in hippocampal glutamate levels potentially account for structural deficits in the hippocampus observed in schizophrenia neuroimaging studies. © 2013 American Medical Association. All rights reserved.