Studies of patients with major depressive disorder (MDD) and schizophrenia (SCH) have revealed reduced hippocampal volumes, but findings have been inconsistent due to sample and measurement differences. The current study sought to measure this structure in a large sample of MDD, SCH, and healthy subjects, using a strict measurement protocol, to elucidate morphological-specific volumetric differences. Patients with treatment-resistant MDD (N = 182) and treatment-resistant SCH with auditory-verbal hallucinations (N = 52), and healthy controls (N = 76) underwent psychiatric assessments and brain MRI. The findings indicate that (1) MDD and SCH patients have reduced total hippocampal volume which was marked in the tails (more so in patients with MDD), (2) region of interest estimation protocols and sample characteristics may help explain volumetric differences between previous SCH studies. © 2010 Wiley Periodicals, Inc., Inc.