We evaluated the handedness of 58 schizophrenia patients and 54 of their relatives, 23 patients with major depression with psychosis and 24 of their relatives, 36 patients with bipolar psychosis and 33 of their relatives, and 119 nonpsychiatric subjects and 42 of their relatives. Computerized tomography measures were also available for a subset of the psychotic patients. The schizophrenia patients were significantly more left-handed than any of the other groups, and increased sinistrality was also associated with larger lateral ventricle to brain area ratios. The relatives of the schizophrenia patients did not significantly differ on handedness from either the relatives of the affective psychosis patients or the nonpsychiatric subjects. Our findings do not support the notion that left-handedness in schizophrenia is genetically influenced. More research with larger family member data sets is warranted to further explore this possibility.