The cerebral effects of iv fluids have not been well defined, particularly the differences between crystalloids and colloids. We thus evaluated the effects of lactated Ringer's (LR) and 6% hetastarch (HES) solutions on brain edema, intracranial pressure (ICP), and cerebral blood flow (CBF) in anesthetized rabbits, using a model of isovolemic hemodilution (IVHD). In this model, arterial blood was removed at a rate of ~2 ml/min for one hour and replaced simultaneously with LR or HES in amounts needed to maintain arterial BP and CVP; Hct decreased from ~40% to ~19%. Thirty-six animals were divided into three groups (n = 12 each): a) IVHD with LR, b) IVHD with HES, and c) maintenance LR without hemodilution. To permit the examination of both acute and delayed fluid effects, each group was further divided into two subgroups (n = 6 each): one in which animals were sacrificed immediately on completion of the one-hour IVHD period (early), and one in which animals were sacrificed 4 h later (late). After sacrifice, brain and skeletal muscle water contents (% H2O) were determined, and the specific gravity (SpGr) of multiple brain samples was measured. Much larger volumes of LR were required to maintain normovolemia as compared with HES, (e.g., totals 203 ± 68 vs 76 ± 18 ml/kg, respectively in late animals) and those given LR had larger increases in body weight and muscle % H2O. There was a significant increase in ICP (3 to 4 mm Hg) with LR that was maximal on completion of IVHD at one hour, but which normalized over the next 4 h. In LR animals sacrificed early, brain % H2O was increased, and tissue SpGr had decreased. However, in the late subgroup, these changes were not present. No changes in ICP, brain % H2O or SpGr were noted in HES animals at either sacrifice time. These results indicate that large amounts of LR can produce measurable but transient increases in both ICP and brain water. However, the contribution of changing colloid oncotic pressure (COP) vs. osmolality are not clear, since COP measurements were not available, and osmolality decreased slightly in LR animals. Nevertheless, it may be advisable to limit the volumes of LR in patients at risk for cerebral edema or intracranial hypertension.