Thallium-201 single photon emission computed tomography (SPECT) is superior to planar imaging for localizing native coronary stenoses, but has not yet been studied for assessing graft patency late after coronary artery bypass graft surgery (CABG). Accordingly, we studied 50 patients (40 males), aged 58 +/- 9 years (mean +/- SD), who presented for evaluation of angina (30 patients), atypical chest pain (20 patients), and other symptoms (9 patients), late after CABG (51 +/- 47 months). Patients with prior myocardial infarction were excluded. The mean ejection fraction was 58 +/- 17%. All patients underwent coronary angiography within 3 weeks of symptom-limited exercise thallium-201 SPECT. There were 119 grafts, of which 48 had > 50% stenosis by angiography. Thallium-201 SPECT detected 40 of these 48 (83%) stenosed grafts. The sensitivity of thallium-201 SPECT for detecting any graft stenosis was higher than that of the exercise electrocardiogram in patients with typical recurrent angina (84% vs 24%, p < 0.0001), as well as in those with atypical symptoms (70% vs 50%, p = 0.0039). The sensitivity of thallium-201 SPECT for correctly localizing the graft stenosis site was 82% for the left anterior descending, 92% for the right coronary, and 75% for the circumflex coronary artery. In conclusion, exercise thallium-201 SPECT is an excellent method to detect and localize graft stenosis late after CABG; it is far superior to the exercise electrocardiogram alone, both in patients with and without typical recurrent angina.