This study was done to evaluate changes of microvascular function under cold stimulation by measuring coronary flow velocities (CFVs) in vasospastic angina (VA) patients using transthoracic Doppler echocardiography (TTDE). 14 patients with VA and 15 healthy controls were included. CFVs were measured at the distal left anterior descending coronary artery by TTDE at baseline and under cold stimulation. Hyperemia was induced by intravenous adenosine infusion (140 microg/kg/min). At baseline, CFVs and coronary flow reserve (CFR) were not different between controls and VA patients. Under cold stimulation, the degree of increment of CFV with adenosine was lower in VA patients than in controls. Comparing baseline with cold stimulation, coronary flow reserve (CFR) increased (3.1+/-0.7 to 3.8 +/-1.0, p=0.06) in controls. In contrast, in VA patients, CFR was decreased (2.8 +/-0.9 to 2.6 +/-0.7, p=0.05) and coronary vascular resistance index markedly increased (0.35 to 0.43, p=0.01). Throughout the study, no patient experienced chest pain or ECG changes. In VA patients, CFR was preserved at baseline, but coronary blood flow increase in response to cold stimulation was blunted and CFR was decreased. These findings suggest that endothelial dependent vasodilation is impaired at the coronary microvascular and the epicardial artery level in VA under cold stimulation.