To evaluate coronary microvascular function and its relation to the genesis of chest pain and ST-segment depression during exercise in patients with syndrome X, pacing-induced changes in transmural myocardial blood flow distribution were quantitatively assessed by 2-dimensional myocardial contrast echocardiography. Of 25 patients with a history of chest pain and normal coronary arteries with the negative ergonovine test, 11 had exercise-induced chest pain and ST-segment depression (syndrome X), and 14 did not (controls). Myocardial blood flow distribution before and after pacing stress was assessed by measuring the ratio of the endocardial to epicardial gray level (ie, endo/epi gray level ratio) in the territory of the left anterior descending coronary artery. Pacing-induced chest pain and ST-segment depression were observed in syndrome X, but not in controls. The endo/epi gray level ratio in syndrome X significantly decreased after pacing (from 0.98+/-0.10 to 0.76+/-0.17, p<0.01), but not in controls (from 0.97+/-0.08 to 0.99+/-0.08, NS). Abnormal myocardial blood flow distribution may play an important role in exercise-induced chest pain and ST-segment depression in these patients.