The sensitivity and specificity of technetium-99m hexakis-2-methoxy-2-isobutyl-isonitrile (sestamibi) single-photon emission computed tomographic (SPECT) imaging for the diagnosis of coronary artery disease were studied in 45 patients admitted to the hospital for clinical suspicion of unstable angina. Only patients without prior myocardial infarction were included and all patients had technetium-99m sestamibi injection and a 12-lead electrocardiogram (ECG) during and less than or equal to 4 h after an episode of chest pain. Coronary angiography performed in all patients during hospitalization showed significant coronary artery disease (greater than or equal to 50% luminal diameter reduction) in 26 of the 45 patients. The SPECT studies obtained after injection of technetium-99m sestamibi during an episode of spontaneous chest pain showed a sensitivity of 96% for the detection of coronary artery disease; the 12-lead ECG obtained at the time of the injection had a sensitivity of 35%. With the patient in the pain-free state, respective sensitivity values were 65% and 38%. Specificity for the radionuclide study was 79% during pain and 84% in the pain-free state; for the ECG, it was 74% both during and between episodes of pain. The site of the perfusion defect corresponded to the most severe coronary artery lesion in 88% of patients. The severity of the perfusion defect correlated with the extent of coronary artery disease: the defect score was 5.3 +/- 3.3 with one-vessel disease, 4.9 +/- 2.8 with two-vessel disease and 10.5 +/- 5.0 with three-vessel disease (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)