Mast cells have been implicated in the pathogenesis of coronary heart disease. They can be activated by immunoglobulin (Ig) E-mediated mechanisms to release powerful mediators affecting local blood flow. We have determined systematically serum IgE concentrations in 100 patients with acute myocardial infarction. There was a consistent pattern of change in serum IgE, characterized by a significant increase on the third and fifth day, peak values on the seventh day, and a gradual decline to initial levels by the end of the third week after infarction. The increase in serum IgE shortly after myocardial infarction was similar to the increase in blood eosinophil count, but was in contrast to serum IgG levels. After infarction, patients with high initial IgE levels (greater than 200 IU/ml) had a greater increase in IgE and less frequent severe complications than those whose initial IgE levels were below 200 IU/ml. In 16 subjects with acute coronary insufficiency without infarction serum IgE levels remained unchanged. It is suggested that in myocardial infarction circulating IgE sensitizes both mast cells of coronary arteries and eosinophils, invading ischemic myocardium; this facilitates release of chemical mediators. Patients with high IgE levels might be protected against complications of infarction because of a favorable ratio of locally released mediators and because of decreased platelet function.