Volumetric magnetic resonance imaging (MRI) studies in obsessive-compulsive disorder (OCD) have reported a smaller volume of the orbitofrontal cortex (OFC) and a larger volume of the thalamus compared with healthy controls. Both of these brain regions are strongly connected; therefore, it may be hypothesized that cortical and thalamic alterations are related. Here, we investigated the relationship between thalamic and orbitofrontal volumes in OCD patients relative to healthy controls. MRI volumetric measurements of the thalamus and the OFC were obtained in 16 OCD patients without comorbidity and 16 comparison subjects matched for age, sex and educational level. Partial correlation analyses that controlled for intracranial volume (ICV) were performed to explore relationships between thalamic and OFC volumes in each group. In order to assess the specificity of this relationship, we conducted similar analyses of the anterior cingulate cortex (ACC) as a non-OFC cortical volume. Finally, by using data from previously published volumetric MRI studies, we conducted a meta-regression to explore the relationships between volume changes in these regions of interest. Results showed that thalamic volumes were significantly negatively correlated with OFC volumes in OCD patients (r=-0.83, p<0.001), but not in healthy subjects (r=-0.15, p=0.59). A significant relationship between thalamic and ACC volumes was found neither in the OCD patients (r=0.03, p=0.91) nor in the comparison subjects (r=-0.23, p=0.40). Furthermore, meta-regression analyses showed that previously reported volume changes in the thalamus were significantly correlated with OFC volume changes (r=-0.71, p<0.05), but not with ACC volume changes (r=0.07, p=0.86). Although our results do not allow for any causal relationship to be established, they suggest that structural alterations of both the thalamus and the OFC are inversely and specifically related in OCD.