Free oxygen radicals are produced after coronary artery occlusion and reperfusion. Polyunsaturated fatty acids are oxidized by free radicals to lipid peroxides. Measurements of plasma malondialdehyde (MDA) formed by the breakdown of lipid peroxides are often used as markers of lipid peroxidation. The effect of intravenous nitroglycerin on plasma MDA levels was studied in 43 patients who received thrombolytic therapy for acute myocardial infarction. Plasma MDA levels in patients were elevated on admission to the hospital compared with healthy controls, and normalized within 48 hours. A greater increase in plasma MDA concentrations after thrombolysis was found in patients with noninvasive signs of reperfusion than in patients judged to have a persistent occlusion. In the 23 patients receiving immediate intravenous nitroglycerin infusion, plasma MDA levels did not change from baseline to 90 minutes (0.92+/-0.22 and 0.92+/-0.23 micromol/L, p=0.99), whereas a significant increase was found in the 20 control patients who did not receive nitroglycerin (from 0.83+/-0.22 to 1.01+/-0.30 micromol/L, p=0.0004) (p=0.036 for the difference between groups). Successful reperfusion after thrombolytic therapy entails increased lipid peroxidation. Intravenous nitroglycerin reduces lipid peroxidation during myocardial ischemia and reperfusion.