Psychiatric disorders have been reported in over 10% of patients with velo-cardio-facial syndrome (VCFS) in long-term follow-up. To further explore the behavioral and psychiatric findings associated with VCFS in adulthood, detailed clinical histories of two patients--one with VCFS who developed a psychotic illness, and one with schizophrenia who was found to have dysmorphological features associated with VCFS--are described in the current report. The observed overlap of physical and psychiatric symptoms in these two patients suggests that VCFS and psychotic disorders may share a pathogenetic mechanism. This could be consistent with a contiguous gene model for VCFS and psychosis, suggesting chromosome 22q11 as a possible candidate region for genetic studies of schizophrenia.