Forced hyperventilation is simple, safe to perform, and can be used as a provocative test for coronary vasospasm. This study assesses whether a vasospastic component of angina might be detected in patients with angiographically "nonobstructive" coronary artery disease by posthyperventilation technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) cardiac imaging. Eleven patients with angiographically nonobstructive coronary artery disease underwent Tc-99m sestamibi SPECT imaging at rest and after forced hyperventilation. Vessel diameters were measured by quantitative angiography before and after forced hyperventilation, and posthyperventilation SPECT images were compared with dipyridamole Tc-99m sestamibi stress images. Forced hyperventilation resulted in a 15% reduction in coronary artery diameter in stenotic segments (p <0.01), and a 17% reduction in adjacent nonstenotic segments (p <0.001). Myocardial uptake of Tc-99m sestamibi in segments perfused by vessels with angiographically nonobstructive stenoses was reduced by 24% following forced hyperventilation (p <0.001) compared with only 4% following dipyridamole (p <0.02). These findings suggest that posthyperventilation Tc-99m sestamibi SPECT imaging in patients with angina pectoris and nonobstructive coronary artery disease may be useful in identifying a vasospastic component of angina.