BACKGROUND: Furosemide and mannitol are used to reduce intracranial pressure, but the impact of furosemide on edema of injured brain is unclear. The authors examined the effects of furosemide and mannitol, alone and in combination, on brain water content in brain-injured rats. METHODS: Anesthetized rats were subjected to a 2.2-atm left hemispheric fluid percussion injury. Two and three-quarters hours later, animals received 0.5, 1, 4, or 8 g/kg mannitol; 8 mg/kg furosemide; a combination of 4 g/kg mannitol plus 4 mg/kg furosemide; or 8 g/kg mannitol plus 8 mg/kg furosemide. One hour later (4 h after injury), plasma osmolality was measured, and hemispheric water content was determined by drying. Other animals were subjected to injury without drug treatment (impact only) or did not undergo injury (control). Pairwise group comparisons regarding the effects of mannitol and furosemide were restricted to only four groups: impact only, 8 g/kg mannitol, 8 mg/kg furosemide, and 8 g/kg mannitol plus 8 mg/kg furosemide. RESULTS: The water content of both hemispheres in the impact-only group was greater than in the control group (left greater than right). Mannitol, 8 g/kg, increased osmolality from 306 ± 4 to 351 ± 6 mOsm/kg (mean ± SD) and reduced water content in the left hemisphere from 80.06 ± 0.84% (impact only) to 78.24 ± 0.73%. Furosemide, 8 mg/kg, had no effect on osmolality or water content. Brain water in animals treated with 8 g/kg mannitol plus 8 mg/kg furosemide did not differ from that seen with 8 g/kg mannitol alone. CONCLUSIONS: Mannitol increased plasma osmolality and reduced water content of the injured and contralateral hemispheres, whereas the authors observed no effect of furosemide when given either alone or in combination with mannitol.