Hypertonic saline was recently introduced as a new hyperosmolar agent for treatment of intracranial hypertension and cerebral edema. It has the potential to cause a rebound phenomenon similar to other osmotic agents. The authors report on two patients with cerebral edema caused by hypertensive intracerebral hemorrhage who were treated with hypertonic saline infusion. Both patients improved clinically after 24 hours of hypertonic saline administration. However, both patients deteriorated clinically, 48 and 96 hours after initiation of therapy, despite continued hypertonic saline administration. Compared with pre-treatment computed tomographic scans, edema volume on repeat scans increased from 131 cc to 262 cc, and from 171 cc to 239 cc in the first and second patients, respectively, despite the lack of change in hematoma volume. Malignant edema formation late in the course of intracerebral hemorrhage after prolonged administration of hypertonic saline may represent a rebound phenomenon of hyperosmolar therapy. Further studies are warranted to identify the occurrence of this phenomenon and the subset of patients susceptible to it.