Objectives. Systemic lupus erythematosus (SLE) can affect multiple organs. Coronary artery disease has received increasing recognition as a major cause of morbidity and mortality in SLE in recent years. The purpose of this study was to evaluate the utility of technetium-99m sestamibi single-photon emission computed tomography (Tc-99m-sestamibi SPECT) in the detection of cardiovascular involvement in SLE patients with non-specific clinical chest symptoms such as chest discomfort and/or dyspnoea and,or occasional palpitation. Methods. Thirty-three SLE female patients (age range: 22-45 yr) with non-specific complaints such as chest discomfort and/or dyspnoea and/or occasional palpitation were investigated using a Tc-99m-sestamibi myocardial perfusion SPECT scan at rest and after dipyridamole infusion in a stress study. The age- and sex-matched healthy group (24 cases) and SLE patients without any cardiovascular symptoms/signs (28 cases) were also included as controls in this study. The results of the uptake pattern of Tc-99m-sestamibi were classified into four types including normal, persistent perfusion defect, reversible perfusion defect and reverse redistribution. Results. Perfusion abnormalities were detected in 27 cases (seven patients had persistent perfusion defects, 15 patients had reversible perfusion defects, one patient had both persistent and reversible perfusion defects, two patients showed a reverse redistribution pattern and two patients had both reversible perfusion defects and a reverse redistribution pattern). The results of the SPECT in the healthy group were all normal, However, perfusion abnormalities were detected in 12 cases in the group of asymptomatic SLE patients. Conclusions. Tc-99m-sestamibi myocardial perfusion SPECT is a useful non-invasive imaging modality to detect cardiovascular involvement in SLE patients with non-specific clinical complaints of heart disease.