BACKGROUND This study was performed to determine the safety and potential efficacy of an intravenous perfluorochemical emulsion (Fluosol) as an adjunct reperfusion therapy aimed at preventing reperfusion injury for patients with acute myocardial infarction. RESULTS Patients (430) were randomized in a prospective open-labeled study, 213 to receive Fluosol and 217 to receive no Fluosol, along with 100 mg of tissue-type plasminogen activator given over 3 hours. Major end points included global ejection fraction, regional wall motion analysis, infarct size as measured by tomographic thallium imaging, and a composite clinical outcome measure. Baseline patient and angiographic characteristics were similar in the two groups. No significant difference in global ejection fraction (52% without Fluosol, 51% with Fluosol) or regional wall motion (-2.4 SD/chord with Fluosol, -2.2 SD/chord without Fluosol) was demonstrated in patients receiving Fluosol versus those not receiving Fluosol, nor was there a significant difference in thallium infarct size. Although Fluosol-treated patients with anterior infarction had an insignificantly lower mean infarct size (18.7% of the left ventricle) compared with patients with anterior infarction not treated with Fluosol (21.2% of left ventricle), this trend was not evident in the median infarct size values (22% versus 17%), left ventricular ejection fraction values (46% without Fluosol, 47% with Fluosol), or regional wall motion (-2.5 SD/chord in both groups). Rates of death and stroke were no different in the two groups; however, patients who received Fluosol experienced less recurrent ischemia. Patients receiving intravenous Fluosol had more transient congestive heart failure and pulmonary edema, perhaps because of necessary fluid administration. There was no difference in hemorrhagic complications between the two study groups. CONCLUSIONS When given with a thrombolytic agent, Fluosol was not associated with improvement in ventricular systolic function, reduction in thallium infarct size, or overall clinical outcome. Fluosol was, however, associated with a reduction in ischemic complications and with an increase in pulmonary edema and congestive heart failure.