To evaluate the impact of anesthetics on the evolution of a cerebral injury, 33 rabbits were subjected to a cryogenic brain lesion, followed by 10 h of anesthesia with 1 MAC halothane or isoflurane (n = 11 each) or with an equipotent dose of pentobarbital (n = 11). The lungs were ventilated to Pa(CO2) = 30-35 mmHg with O2/air and normothermia was maintained. Intracranial pressure (ICP), mean arterial pressure (MAP), central venous pressure (CVP), arterial blood gases, and pH, osmolality, and other blood chemistries were recorded. Fifteen minutes after surgery, a left parietal injury was produced with liquid N2. A MAP > 70-75 mmHg was maintained throughout the study, using angiotensin II as needed, and CSF was removed if severe intracranial hypertension (ICP > 30 mmHg) threatened to reduce cerebral perfusion pressure (CPP = MAP-ICP) below 40 mmHg. 10 h after injury, the animals were killed, and edema formation assessed by: A) the wet weight of the two hemispheres; B) water content (%H2O; wet-dry weight) of the posterior aspect of the hemispheres; and C) specific gravity (SpGr) of tissue samples taken adjacent to and distant from the lesion. Animals given pentobarbital had higher MAP's until 3 h after the lesion had been induced. There were no subsequent intergroup differences in MAP, and no differences at any time in CVP, Pa(O2), Pa(CO2), pH, total fluids, or urine output. ICP increased in all animals, but with no significant intergroup differences (ICP in halothane animals was numerically lower). There were no clear differences in the incidence of ventricular drainage (1 halothane, 5 isoflurane, 3 pentobarbital; P = 0.16). In spite of CSF drainage and angiotensin, CPP values fell below 40 mmHg in six animals (2 halothane, 3 isoflurane, 1 pentobarbital). These were not used for subsequent edema measurements. Wet weights and %H2O of the left (lesioned) hemisphere were greater than on the right, but with no intergroup differences. SpGr of tissue adjacent to the injury was lower (more edema) than in other brain areas. SpGr in three sections, however, and average hemispheric SpGr values for the left hemisphere, were higher (less edema) in animals receiving halothane. The authors conclude that halothane anesthesia resulted in less edema formation in the vicinity of the injury. While this was not conclusively reflected in other indices of lesion severity, intracranial hypertension may also have been less severe (based on ICP measurements and the need for ventricular drainage). These results indicate that neither pentobarbital nor isoflurane offer any advantages over halothane with respect to the development of edema after an experimental brain injury.