Involvement of the brain is one of the most important complications of Behçet's disease (BS). It is difficult to diagnose, however, because of the lack of effective imaging methods. METHODS Thirteen BS patients with neuropsychiatric symptoms or signs [Neuro-Behçet's syndrome (NBS)] were included in this study. We combined two routine brain imaging modalities-brain SPECT with 99mTc-hexamethyl propyleneamine oxime (HMPAO) and brain MRI-with clinical manifestations to diagnose brain involvement. RESULTS Technetium-99m-HMPAO brain SPECT findings were abnormal in 100% (13/13) of patients. Brain MRI findings were abnormal in 31% (4/13) of patients. Gray matter was involved more commonly than white matter. In the gray matter, the cerebral cortex was the most commonly involved area and the cerebellum was the least commonly involved area in NBS. CONCLUSIONS SPECT is a more sensitive and useful tool in detecting brain involvement in NBS patients compared with brain MRI. The combination of HMPAO and MRI is necessary to detect brain lesions in both gray and white matter in NBS.