Most patients with chronic Chagas' heart disease complain of chest pain. The pathophysiology of this symptom is unknown, although myocardial necrosis and fibrosis are frequent necropsy findings and cardiac autonomic impairment is a prominent feature of the disease. To evaluate the possibility of an ischemic cause for these abnormalities in 23 patients (18 men, aged 32 to 60 years, mean 42) with chronic Chagas' disease complaining of chest pain, thallium-201 myocardial scintigraphy was performed after maximal effort and 4-hour redistribution. Regional wall motion was assessed by radionuclide and contrast angiography. Heart rate responses to sinus respiratory arrhythmia, atropine, phenylephrine and Valsalva maneuver were evaluated in all patients and in 22 normal control subjects. Coronary angiography was performed in 16 patients. Only 1 patient had chest pain and no ischemic electrocardiographic changes occurred in any case during the effort test. Scintigraphic analysis of 7 segments per patient showed perfusion defects in at least 1 segment in all patients. Of 161 myocardial segments 16 showed fixed, 10 reversible, and 22 paradox defects (reverse redistribution). The majority (75%) of the fixed perfusion defects occurred in dyssynergic regions, whereas reverse redistribution predominated in regions with normal wall motion (82%). The reversible defects were present in normal or mildly hypokinetic regions. Markedly impaired parasympathetic cardiac control was present but no significant coronary abnormalities were seen in any of the 16 patients undergoing angiography. It is concluded that whereas fixed defects are likely to correspond to fibrotic or necrotic lesions, reversible and paradox perfusion defects may be caused by regional flow or metabolism derangements, possibly related to abnormal parasympathetic control of the coronary microcirculation.