OBJECTIVE: To determine whether intravenous mannitol administration reduces intracranial pressure (ICP) in a cat model of brain edema by changing serum osmolality. DESIGN: Prospective, controlled study. SETTING: Pediatric intensive care unit laboratory in a university hospital. INTERVENTIONS: Intraparenchymal ICP monitors were placed in 12 adult cats which subsequently underwent 60 min of continuous arteriovenous hemofiltration with countercurrent dialysis (CAVH-D), using sterile water with potassium chloride as a dialysate. The ultrafiltrate was replaced with a hypotonic solution causing a rapid reduction in serum osmolality while maintaining a euvolemic state. In six cats (control group) no further interventions were instituted, while in the six other cats (mannitol group) 1g/kg mannitol was administered intravenously immediately after CAVH-D had been discontinued. ICP was monitored continuously, and serum osmolality was determined at 15-min intervals during CAVH-D and for 30 min thereafter. RESULTS: ICP increased significantly in both the control and mannitol groups during 60 min of CAVH-D. After CAVH-D, ICP was reduced in the mannitol group while ICP remained significantly higher in the control group. An inverse linear correlation was demonstrated between serum osmolality and ICP values in the control group throughout the experiment, as well as during the first 60 min in the mannitol group. However, no such correlation existed in the mannitol group after mannitol administration, as no significant changes in serum osmolality were observed while a marked reduction in ICP values occurred. CONCLUSION: Mannitol is effective in reducing increased ICP in this model of euvolemic brain edema. However, 15 min after mannitol administration, no relationship between a continued decrease in ICP and a change in serum osmolality could be established. We postulate that the beneficial effect on ICP by mannitol outlasts its possible instantaneous and short-lived effect on serum osmolality.