Seventy-three patients with angina pectoris and 20 with atypical chest pain, who underwent coronary angiography, were examined by single-photon emission computed thallium tomography (TI-SPECT) using a combined dipyridamole-handgrip stress test. Perfusion defects were detected in 78 of 81 patients with angiographically significant coronary artery disease (CAD) (sensitivity 96%). In 9 of 12 patients without CAD, the thallium images were normal (specificity 75%). Thirty-five patients with CAD were reexamined by TI-SPECT using a dynamic bicycle exercise stress test. The sensitivity of the dipyridamole-handgrip test did not differ from the bicycle exercise test in diagnosing the CAD (97% vs 94%). Multiple thallium defects were seen in 19 of 22 (86%) patients with multivessel CAD by the dipyridamole-handgrip test but only in 14 of 22 (64%) by the bicycle exercise test. Noncardiac side-effects occurred in 17 of 93 (18%) patients after dipyridamole infusion. Cardiac symptoms were less common during the dipyridamole-handgrip test than during the bicycle exercise (15% vs 76%, p less than 0.01). These data suggest that the dipyridamole-handgrip test is a useful alternative stress method for thallium perfusion imaging, particularly in detecting multivessel CAD.