Background and Purpose—The goal of this study was to examine the effects of hypertonic saline on cerebral blood flow (CBF) in poor-grade patients with subarachnoid hemorrhage.Methods—We administered 23.5% hypertonic saline (2 mL/kg IV) 1 time to 10 patients, 2 times to 7 patients, and 3 times to 1 patient. All patients had transcranial Doppler (TCD), intracranial pressure (ICP) monitoring, and analysis of serum sodium and osmolality; 6 had xenon CT (XeCT). Data were used to characterize the changes in CBF, cerebral vascular resistance (CVR), ICP, cerebral perfusion pressure (CPP), and potential rheological mechanisms of action.Results—In the first treatment episode, CPP increased 26.8% (P=0.0003, at 28.3 minutes) from a rise in mean arterial blood pressure (ABP) of 10.5% (P=0.02, at 22.2 minutes) and a fall in ICP (−74.7%,P=0.002, at 60.0 minutes). Flow velocity (FV) of the middle cerebral artery increased 70.8% (P=0.00005, at 20.0 minutes), resulting in a corresponding fall in estimated CVR (−26.6%,P=0.01, at 16.3 minutes). The half-lives of effects on ABP, CPP, ICP, FV, and estimated CVR were 20.0, 53.6, 139.1, 42.7, and 27.1 minutes, respectively. In the second treatment episode, all these parameters had the same response except estimated CVR, which did not reach statistical significance. XeCT confirmed the increase in CBF (22.9%,P=0.02) without regional differences. A fall in CBF after hypertonic saline was identified in only a single region of interest in a patient in whom baseline flow was low but not infarcted. Serum sodium rose by 11.4 and 8.8 mmol/L, and osmolality rose by 26.7 and 16.3 mosm/L in the first and second treatment episodes, respectively. Hemoglobin decreased by 0.7 and 0.6 g/L and hematocrit decreased by 1.9% and 2.4% in the first and second treatment episodes, respectively.Conclusions—We found that 23.5% hypertonic saline increases CBF in poor-grade patients with subarachnoid hemorrhage. These effects are associated with improved indexes of blood rheology. Potential therapeutic benefits are discussed.