Central nervous system (CNS) involvement in patients with systemic lupus erythematosus (SLE) is often difficult to evaluate because of protean neuropsychiatric (NP) manifestations and lack of reliable diagnostic markers. In the reported study the role of single-photon emission tomography (SPET) with technetium-99m hexamethylpropylene amine oxime (HMPAO) in the evaluation of CNS involvement in SLE was assessed and the relations between SPET perfusion defects, EEG examination, magnetic resonance imaging (MRI) findings and clinical presentation were examined. Twenty SLE patients with different NP manifestations were studied. Multiple areas of hypoperfusion, especially in the territory of the middle cerebral artery, were demonstrated by SPET analysis in all 20 patients. The number of hypoperfused areas and the degree of hypoperfusion, expressed by an asymmetry index (AI), were more marked in patients with multiple NP manifestations. MRI and EEG evaluations were positive for 14 of 18 and for 12 of 20 patients, respectively. In the patients with positive SPET and MRI, 87 MRI focal lesions and 63 hypoperfused areas were found, and for 51 of these 63 at least one MRI lesion was found in the same anatomical region. SPET examination of patients with a normal EEG showed fewer hypoperfused areas and a lower degree of asymmetry compared to patients with an abnormal EEG. SPET of patients with focal EEG abnormalities showed more hypoperfused areas (difference not statistically significant) and a higher AI than did SPET of the patients with diffuse EEG abnormalities. Seven of 11 anatomical regions with focal EEG abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)