This study evaluated the effects of different iso-osmolal solutions used for intravascular volume replacement on post-ischemic cerebral edema. Fasted Sprague-Dawley rats underwent 10 min of severe (near-complete) forebrain ischemia (bilateral carotid artery occlusion and hemorrhagic hypotension). At the completion of ischemia, 40% of the estimated total blood volume was replaced by iso-osmolal saline, 6% hetastarch, or blood. Plasma osmolality remained similar between groups throughout the experiment, while saline infusion resulted in a significant but transient decrease in colloid oncotic pressure. At 1.5 h, 6 h, and 24 h post-ischemia (PI), specific gravity was determined for tissue samples taken from the hippocampus, caudoputamen, and neocortex. Normal values were obtained from rats receiving anesthesia only. The ischemic insult resulted in a significant increase in regional water content at 1.5 h PI in animals receiving blood. These values were not different from rats receiving saline or hetastarch. At 6 h PI, partial resolution of the edema was observed, with no differences in regional specific gravity occurring between fluid groups. At 24 h PI, again, no difference between fluid regimens was seen in the hippocampus or neocortex. However, in the caudoputamen, hetastarch produced a significant increase in water content relative to both saline and blood. With that exception, the authors' results indicate that early post-ischemic cerebral edema remains generally independent of iso-osmolal fluids used for resuscitation in this model of global ischemia.