The purpose of this study was to compare two different doses of dipyridamole as a pharmacologic stress test for 201Tl imaging. METHODS Twenty-four patients with significant coronary artery disease (15 had undergone a coronary angiogram and 9 had undergone a previous 201Tl study with a significant lesion) were prospectively studied. Within 1 wk, all patients underwent two 201T-dipyridamole myocardial planar studies, one using a standard dose (STD) and the other, a high dose (HIGH) of dipyridamole. The protocol order was randomly assigned. The STD protocol used a dose of 0.14 mg/kg/min for a duration of 4 min (0.56 mg/kg), and the HIGH protocol used a dose of 0.14 mg/kg min for a duration of 6 min (0.84 mg/kg). The 201Tl was injected 3 min after the end of the dipyridamole infusion. Images, obtained 5 min and 4 hr later, were interpreted (divided into five segments each) by three blinded observers. RESULTS The STD protocol showed normal, ischemia and scar in 252, 91 and 17 segments, respectively. The HIGH protocol detected 232, 118 and 10 segments, respectively. A side-by-side evaluation was done to evaluate the defect extent subjectively, which was greater with HIGH in 14, equal in six and smaller in four patients. One or more side effects were seen in 14 patients with STD and in 19 with HIGH. Increased heart rate (8 bpm for STD and 19 bpm for HIGH, p < 0.001) was the only significant change seen in the hemodynamic parameters. CONCLUSIONS This preliminary study indicates that a high dose of dipyridamole seems to be safe and can be helpful to increase the sensitivity of 201Tl imaging.