Diffusion tensor imaging has been highlighted as a non-invasive tool to explore neural connectivity in vivo. Several studies have suggested disorganization of the neural network (circuitry) including the thalamo-prefrontal connection in schizophrenia. Recent research using post-mortem brains showed that the superior occipitofrontal fasciculus (SOFF) fibers extended to the thalamus. We postulated that the SOFF has some relationship with the anatomical structural components of the thalamo-prefrontal circuitry. We quantitatively assessed the diffusion abnormalities of the SOFF using diffusion tensor tractography (DTT) in schizophrenia. Nineteen male patients with schizophrenia and 20 age-matched normal controls were studied. DTT of the SOFF (DTT-SOFF) was visualized using free software (dTV II/VOLUME-ONE), and we performed tract-specific measurement of the fractional anisotropy (FA), then calculated the apparent diffusion coefficient (ADC) of the DTT-SOFF. Tractography and tract-specific analysis of the SOFF were successfully performed in all subjects. All tracts appeared to be connecting the prefrontal area to the thalamus. The mean FA value of patients with schizophrenia [0.376 (S.D. 0.030)] was significantly lower than that of controls [0.432 (S.D. 0.032)], and the ADC value of patients with schizophrenia [0.771 (x10(-3) mm(2)/s) (S.D. 0.041)] was significantly higher than that of controls [0.726 (x10(-3) mm(2)/s) (S.D. 0.027)]. Our results suggest that the so-called SOFF may be a structural component connecting the prefrontal area to the thalamus and that it is deteriorated in schizophrenia.