Recent evidence suggests that postischemic myocardial dysfunction ("stunning") may be mediated by oxygen free radicals. Various studies have reported the beneficial effects of antioxidants in ischemia-reperfusion injury. The aim of this study was to assess the effect of N-acetylcysteine (NAC) treatment on oxidative stress, infarct size, and left ventricular (LV) function, as adjunct therapy in myocardial infarction (MI). Patients with acute MI received either 15 g NAC infused over 24 h (n = 15) or no NAC (n = 15), combined with streptokinase. Peripheral venous blood was serially sampled to measure creatine kinase (CK)-MB levels. Plasma malondialdehyde (MDA) level was measured at admission and after 4 and 24h. Echocardiography was performed within 3 days of MI and after 3 months. At admission, plasma MDA levels were not different between the groups. In the NAC-treated patients plasma MDA levels decreased, whereas in the nontreated NAC patients MDA levels increased at 4 and 24h (P < 0.01 and P < 0.001, respectively). Left ventricular ejection fraction was higher (P < 0.05) and LV end-systolic and end-diastolic diameters were lower (P < 0.001 and P < 0.001) in patients receiving NAC on day 3. Left ventricular wall motion score index was significantly lower in patients treated with NAC on day 3 (P < 0.05). Left ventricular diastolic parameters were not different whether patients were treated with NAC or not. No difference in reduction of infarct size was detected between the groups according to CK-MB levels. It was thus demonstrated that administration of NAC in combination with streptokinase significantly diminished oxidative stress and improved LV function in patients with acute MI. These encouraging results would justify the performance of a larger controlled study.