OBJECTIVE: The antioxidant potential N-Acetylcysteine (NAC) and its improvement of posttraumatic mitrochondrial dysfunction have been reported. This study investigated the effect of NAC on posttraumatic changes after controlled cortical Impact (CCI) injury. DESIGN AND SETTING: Prospective randomized controlled animal study. METHODS: A moderate left focal cortical contusion was induced using CCI. Either NAC (163 mg/kg bw) or physiological saline was administered intraperitoneally immediately and 2 and 4 h after trauma. Blood gases, temperature, mean arterial blood pressure (MABP), and intracranial pressure (ICP) were monitored. Twenty-four hours after trauma brains were removed and either posttraumatic edema was quantified gravimetrically (n=24], or contusion volume was determined morphometrically using slices staining and computerized image analysis (n=24]. Laser Doppler flowmetry was used to assess pericontusional cortical perfusion before trauma, 30 min and 4 and 24 h after trauma (n=14]. MEASUREMENTS AND RESULTS: Physiological parameters remained within normal limits. ICP measurements and water content in traumatized hemispheres did not differ between the groups. Relative contusion volume of the left hemisphere was slightly but nonsignificantly diminished in NAC-treated animals (4.7+/-0.4% vs. 5.9+/-0.5% in controls). In both groups pericontusional perfusion was significantly reduced at 4 h followed by a state of hyperperfusion at 24 h with no differences between the groups. CONCLUSIONS: Despite previously reported neuroprotective abilities of NAC, no positive effect on posttraumatic perfusion, brain edema formation, or contusion volume after focal brain injury was observed in this study.