Background. 22q11 Deletion Syndrome (22qDS) is a genetic syndrome associated with 22q11.2 deletions and high rates of schizophrenia. Based on brain structural findings in children with 22qDS and adults with schizophrenia compared to controls, we hypothesized that adults with 22qDS and no psychosis (22qDS-NP) would have: (1) smaller ventricular and larger gray matter volumes than adults with 22qDS and schizophrenia (22qDS-SZ) and (2) larger ventricular and smaller gray matter volumes than controls. Method. Analysis of variance and t-tests were performed on MRI scan data corrected for total intracranial volume from 22qDS-NP (n = 7), age- and sex-matched controls (n = 7) and 22qDS-SZ (n = 12) groups. Results . Ventricular volumes for 22qDS-NP were smaller than 22gDS-SZ (p = 0.004) and larger than Control groups (p = 0.04). Whole brain gray matter volumes for 22gDS-NP were intermediate to 22qDS-SZ and control subjects (p > 0.14). Conclusions. Enlarged ventricles in this small sample suggest that increased power to detect differences between 22gDS-SZ and 22gDS-NP adults may lead to the identification of brain structure findings related to the expression of schizophrenia in 22qDS.