To evaluate the usefulness of a dipyridamole stress thallium-201 (Tl-201) perfusion scan in detecting myocardial involvement in systemic sclerosis we performed Tl-201 scans, electrocardiograms (ECG), and echocardiograms (UCG) on 24 patients with systemic sclerosis (11 diffuse type, 13 limited type) sequentially selected randomly over an 8-month period, and compared the findings. Cardiac catheterization, coronary angiography (CAG), and right ventricular endomyocardial biopsy were performed as necessary. Of the 24 patients, Tl-201 scans revealed fixed defects (FDs; myocardial fibrosis) and/or reversible defects (RDs; myocardial ischemia) in nine patients, whereas ECG and UCG revealed defects in four and three patients, respectively. Biopsy specimens obtained from the three patients with FDs also showed both ECG and UCG abnormalities indicative of myocardial fibrosis despite their normal appearance with CAG. Autopsy findings on the heart of a patient who died of acute heart failure showed myocardial fibrosis predominantly in the left anteroposterior wall. This was consistent with the FDs area detected using the Tl-201 perfusion scan. In a patient with chronic heart failure, left ventriculography showed a decrease in the anterior wall motion of the left ventricle which coincided with the FDs area in the Tl-201 perfusion scan. In conclusion, dipyridamole stress Tl-201 scanning is useful for evaluating myocardial involvement in systemic sclerosis.