The aim of this study was to detect brain functional deficits in patients with Behçet's disease (BD) and signs or symptoms of central nervous system (CNS) involvement at different times in their clinical history. A total of 24 patients aged 20 to 53years (median age 39years; 20 women, four men) with Behçet's syndrome fulfilling the diagnosis as defined by the syndrome classification were enrolled in this study. Single-photon emission computed tomography (SPECT) with ^99mTechnetium (Tc)-hexamethylpropyleneamine oxime (HMPAO) as the perfusion tracer was performed to detect brain lesions. The results of ^99mTc-HMPAO brain SPECT scans showed impaired perfusion in all cases with neurological complaints (24 out of 24, 100%). Temporal lobes and basal ganglia were the most common areas with such lesions. In contrast, brain MRI and CT images were normal or non-specific in all cases. In conclusion, ^99mTc-HMPAO brain SPECT imaging is a powerful and sensitive tool for disclosing brain involvement in numerous clinical situations, even including patients with subtle neurological symptoms/signs such as headaches and dizziness. It is also a useful modality for evaluating the effects of treatment and disease monitoring to prevent CNS damage.