Increased plasma and cerebral glutamate levels may contribute to posttraumatic edema formation. Since volatile anesthetics elevate plasma amino acid concentrations, the influence of isoflurane on arterial plasma glutamate levels and brain edema formation was investigated in brain-injured rats. Rats were anesthetized with chloral hydrate (380 mg/kg i.p.) or isoflurane (1.2-2.0 vol%) for four hours following controlled cortical impact injury. Isoflurane significantly increased arterial glutamate levels compared to chloral hydrate (124 +/- 12 vs. 60 +/- 5 microM; p < 0.005). At eight hours after trauma, water content was significantly increased in the traumatized hemisphere compared to the non-traumatized side (p < 0.005). In addition, four hours of isoflurane anesthesia caused a significant increase in brain water content of both hemispheres compared to chloral hydrate (80.1 +/- 0.1 vs. 79.6 +/- 0.1%; p < 0.005). Prolonged isoflurane anesthesia is associated with a significant increase in arterial plasma glutamate levels and brain water content. This increase in brain water content must be considered when performing prolonged isoflurane anesthesia.