Objective. Accelerated atherosclerosis is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Altered coronary microvascular function may act as a marker of changes that predispose to the development of significant coronary vascular disease. The purpose of this study was to compare coronary flow reserve (CFR) in a group of premenopausal women with SLE and a group of age-, sex-, and race-matched healthy control subjects. Methods. Coronary flow velocity in 18 premenopausal women with SLE (mean ± SD age 29.4 ± 5.9 years) and 19 matched healthy controls (mean ± SD age 28.2 ± 4.3 years) was assessed by transthoracic Doppler echocardiography after an overnight fast. The CFR was calculated as the ratio of hyperemic to baseline coronary blood flow velocity in the left anterior descending coronary artery. Hyperemia was induced by intravenous administration of adenosine triphosphate. Results. The mean ± SD duration of SLE was 8.2 ± 7.2 years (range 0.25-25 years), and the mean ±SD score on the Systemic Lupus Erythematosus Disease Activity Index was 11.0 ± 5.3 (range 4.0-21.0). Adequate recordings of flow velocity in the left anterior descending artery under both conditions were obtained using an ultrasound procedure in all study subjects. CFR was significantly lower in SLE patients as compared with control subjects (mean ± SD 3.4 ± 0.8 versus 4.5 ± 0.5; P < 0.0001). Conclusion. These findings provide evidence that coronary vasomotor function is impaired in patients with SLE and support the notion that many of these young patients have subclinical coronary artery disease.