Symptomatic differences have been reported between patients with familial and sporadic schizophrenia. The present study examined neuroanatomical differences between the two subgroups and their parents using voxel-based morphometry. High-resolution T1-weighted images were obtained using 3 Tesla magnetic resonance imaging from 20 patients with schizophrenia (familial subgroup, n=10; sporadic subgroup, n=10), 20 of their parents (familial subgroup, n=10; sporadic subgroup, n=10) and 20 healthy volunteers. Gray matter density (GMD) was compared between groups on a voxel-by-voxel basis. Compared with the sporadic patients, the familial patients had significantly reduced GMD in the thalamus bilaterally. Reduction of GMD in bilateral thalami was also found in familial parents in comparison with sporadic parents. Compared with controls, both familial and sporadic patients had lower GMD involving bilateral insula, right temporal lobe, right occipital lobe, left lenticular nucleus and right cerebellum. However, only familial patients showed lower GMD than controls in the right thalamus. Compared with controls, only familial parents showed lower GMD in the right insula extending to the right temporal lobe and the right parietal lobule. The present data suggest that familial schizophrenia is associated with more severe structural abnormalities than sporadic schizophrenia, especially in the thalamus.