In patients with systemic lupus erythematosus, involvement of the cardiovascular system is the third leading cause of death. However, although autopsy studies have demonstrated a high incidence of abnormalities in both the myocardium and coronary vessels, clinical manifestations have been reported in only a small percentage of cases. The aim of this study was to evaluate myocardial perfusion in asymptomatic lupus patients using technetium-99m sestamibi single-photon emission tomography (SPET). Twenty-eight patients without overt cardiac involvement and risk factors were studied with 99mTc-sestamibi SPET at rest and after dipyridamole infusion. Perfusion abnormalities were detected in 18 cases: six had persistent defects, three had reversible defects, seven had both persistent and reversible defects, and two showed rest defects which normalized on dipyridamole images ("reverse redistribution pattern"). Coronary angiography was performed in eight patients with positive 99mTc-sestamibi SPET, and showed normal epicardial vessels in all the cases. These results indicate that 99mTc-sestamibi SPET reveals a high prevalence (18 out of 28 patients in this study, i.e. 64%) of myocardial perfusion abnormalities in asymptomatic lupus patients, probably due to the primary immunological damage of this autoimmune disease. In conclusion, rest/dipyridamole 99mTc-sestamibi SPET can be a useful non-invasive method to identify subclinical myocardial involvement in systemic lupus erythematosus, and patients potentially at risk of later cardiac events.