In view of a growing interest in the resuscitative use of hypertonic saline solutions, the authors have examined the cerebral effects of isovolemic hemodilution carried out over 1 hour (hematocrit decreased from 40% to 20%, stable arterial and right arterial pressures), using a hypertonic lactated Ringer's solution (HT-LR: Na+ 252 mEq/liter, osmolality 480 mOsm/liter). Experiments were carried out in anesthetized ventilated rabbits. Measured variables included cerebral blood flow (using the H2 clearance method), intracranial pressure (ICP), the electroencephalogram, spinal cord and skeletal muscle water content (%H2O), and the specific gravity of small (10- to 30-mg) tissue samples taken from different areas of the left hemisphere (including the cortex, thalamus, internal capsule, and hippocampus). The changes produced by HT-LR were compared with those seen in both undiluted control animals and in rabbits hemodiluted with normal saline (Na+ 155 mEq/liter, osmolality 310 mOsm/liter). The results demonstrate that hemodilution with HT-LR leads to the expected increases in serum Na+ and osmolality (158 ± 6 mEq/liter and 320 ± 5 mOsm/kg, respectively, mean ± standard deviation) and that these were accompanied by reductions in the %H2O of all cerebral and extracerebral tissues, increases in the specific gravity of all tissue regions studied, and a decrease in ICP (1.9 ± 0.7 mm Hg). By contrast, rabbits with hemodilution by normal saline showed no changes in either %H2O or specific gravity, but had significant increases in ICP (3.3 ± 1.3 mm Hg). Cerebral blood flow increased in all animals hemodiluted with either HT-LR or normal saline by a combined average of +29 ml/100 gm/min. Although these studies were performed in neurologically normal animals, the combination of cerebral changes seen with HT-LR (cerebral dehydration, less peripheral edema, decreased ICP but with increased cerebral blood flow) suggests that this approach may have some advantages over the use of isotonic fluids, and may have some utility in the resuscitation of head-injured patients.