BACKGROUND: Moderate hypothermia (MH) is a therapeutic approach for ischemic stroke as well as cardiac arrest. Two different technical strategies of ventilation during MH called alpha- and pH-stat dramatically influence cerebral blood flow (CBF). In turn this might influence neuronal damage and intracranial pressure (ICP). Therefore, effects of ventilation on CBF and ICP were measured in patients undergoing MH because of large ischemic stroke to address optimal ventilation management. METHODS: Eight patients (n = 8) with large ischemic stroke in the territory of the middle cerebral artery (MCA) were treated by MH of 33 degrees C within 24 h after symptom onset. MH was applied at least for 72 h. Each day, patients were ventilated repetitively with either alpha-stat or pH-stat for 60 min periods. Alpha-stat was applied between the measurements. ICP, CBF, and mean arterial blood pressure (MABP) were measured. The xenon clearance method was used to assess CBF at the bedside. RESULTS: There were no significant differences between ICP values for alpha-stat or pH-stat during days 1 and 2 after induction of hypothermia. However, ICP was higher in the pH- as compared to the alpha-stat group (P < 0.05) and exceeded a mean of 20 mmHg on day 3. pH-stat led to a significant increase of CBF in all measures (P < 0.05), while MABP was unaffected. CONCLUSIONS: pH-stat implies a better CBF to the injured brain, while it might be dangerous by elevating ICP in more subacute stages.