Five term and two premature newborn infants were referred for respiratory distress and congestive heart failure, and were found to have electrocardiographic Q or ST-T abnormalities suggesting ischemia. Echocardiographic and/or hemodynamic assessment excluded anatomic heart disease in six infants. In three infants, moderate or severe hemodynamic impairment within 36 hours of age was suggested by these studies. Myocardial perfusion images in all patients showed very poor myocardial uptake of thallium 201, compatible with global myocardial ischemia. Infants of similar age with myocarditis, or with congenital heart disease and congestive failure, had normal myocardial uptake. Rapid clinical improvement occurred within three to seven days. Two to five months later, all infants were well. Two had persistent electrocardiographic abnormalities but repeat thallium 201 imaging in six demonstrated almost normal myocardial uptake. These data provide further evidence that perinatal respiratory distress may be associated with myocardial dysfunction and congestive heart failure in some infants without anatomic heart disease, and suggest that myocardial dysfunction in these infants is associated with global myocardial ischemia, most of which is transient. The timing and nature of the insult causing the ischemia are unclear.