The hemoglobin-oxygen affinity of pure hemoglobin was studied in 11 patients with signs of myocardial ischemia or acute necrosis and in 12 controls. Additionally, the hemoglobin of a moderate and a heavy cigarette smoker without evidence of cardiovascular disease was studied. Under physiological pH conditions, the hemoglobin gave up oxygen in an abnormal manner in all except the 12 controls.In all control subjects and patients, the arterial saturation was normal and blood pH values were within normal limits. Electrophoretic abnormality was not found in any of the subjects studied. It is thus demonstrated that hemoglobin may be physicochemically abnormal without electrophoretic abnormality. From a functional point of view, the hemoglobin's abnormal response to changes in oxygenation may result from altered proton-binding properties of the hemoglobin molecule. That such "abnormal" hemoglobin could contribute to the paradox of myocardial ischemia or necrosis occurring in the presence of full arterial saturation and patent coronary arteries is not certain from these studies.Further studies investigating the role of abnormal hemoglobin-oxygen affinity in the pathophysiology of myocardial ischemia or necrosis appear justified and necessary.