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Hippocampal volume reduction and decreased memory skills form a characteristic neurofunctional alteration observed in schizophrenia. Individuals affected with 22q11.2 deletion syndrome (22q11DS), while exhibiting memory deficits throughout development, are also at high risk for developing schizophrenia. The present study sought to investigate hippocampal volume reduction as separate of global grey matter reduction in a large, independent sample of individuals with 22q11DS. Volumetric data from structural magnetic resonance imaging was obtained for 43 individuals affected with 22q11DS, aged 6–39 years of age, as well as for 40 healthy individuals matched for age and gender. Drawing of the amygdala was included to enhance the delineation of the hippocampus, and circumscription of both the amygdala and the hippocampus were executed using an increased resolution matrix. After controlling for total grey volume reductions observed in affected individuals, a significant decrease in hippocampus volume was observed in the 22q11DS group, driven by significant bilateral volumetric reduction of the body of the hippocampus. These results are discussed in reference to memory and cerebral alterations already reported in 22q11DS. Further, the specific implications of hippocampus body volume reduction are outlined in light of its anatomical relationships and its function in memory. Finally, reduction of hippocampal volume in 22q11DS is examined in the context of psychiatric risk status associated to the deletion.