Loss of normal fronto-occipital cerebral asymmetry has been reported in patients with schizophrenia and also in their well relatives from multiply affected families, suggesting a relationship with susceptibility genes. We sought to confirm this relationship in a family study of patients with schizophrenia and their unaffected relatives of presumed differing genetic risk. MRI scans were carried out on 25 probands from families multiply affected with the disorder, and 36 of their unaffected relatives, 34 probands from families with no other affected members, 42 of their unaffected relatives, and 76 controls. Volumetric measurements of prefrontal, premotor, sensorimotor and occipitoparietal regions were obtained from which a measure of fronto-occipital torque was derived. There were no significant differences in measurements of fronto-occipital torque between the subject groups. Both schizophrenic probands and their relatives displayed the normal pattern of cerebral asymmetry, with larger right than left frontal regions and a larger left than right occipitoparietal region. Our findings failed to confirm an association between loss of fronto-occipital torque and genetic liability for schizophrenia and also failed to replicate the previously reported association between loss/reversal of fronto-occipital asymmetry and schizophrenia.