Several but not all MRI studies have reported volume reductions in the hippocampus and dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. Given the high prevalence of smoking among schizophrenia patients and the fact that smoking has also been associated with alterations in brain morphology, this study evaluated whether a proportion of the known gray matter reductions in key brain regions may be attributed to smoking rather than to schizophrenia alone.We examined structural MRI data of 112 schizophrenia patients (53 smokers and 59 non-smokers) and 77 healthy non-smoker controls collected by the MCIC study of schizophrenia. An automated atlas based probabilistic method was used to generate volumetric measures of the hippocampus and DLPFC. The two patient groups were matched with respect to demographic and clinical variables.Smoker schizophrenia patients showed significantly lower hippocampal and DLPFC volumes than non-smoker schizophrenia patients. Gray matter volume reductions associated with smoking status ranged between 2.2% and 2.8%. Furthermore, we found significant volume differences between smoker patients and healthy controls in the hippocampus and DLPFC, but not between non-smoker patients and healthy controls.Our data suggest that a proportion of the volume reduction seen in the hippocampus and DLPFC in schizophrenia is associated with smoking rather than with the diagnosis of schizophrenia. These results may have important implications for brain imaging studies comparing schizophrenia patients and other groups with a lower smoking prevalence.