Using the technique of ventriculocisternal perfusion, resistance to reabsorption of cerebrospinal fluid (Rss) was calculated from determinations of the rate of reabsorption of cerebrospinal fluid (Vss) at differing cerebrospinal fluid pressures in dogs. Rawas examined during prolonged anesthesia (5.0–6.0 h) with enflurane (2.2%, end expired) or isoflurane (1.4%, end expired). Compared with previously reported normal values for Rain dogs (220–224 cmH2O · ml-1· min), enflurane increased Rato 274 ± 4 cmH2O · ml-1· min (mean ± SEM), and isoflurane decreased Rato 104 ± 1 cmH2O · ml-1· min. The alterations of cerebrospinal fluid (CSF) dynamics caused by enflurane, namely increase of both Raand the rate of production of cerebrospinal fluid (Vss), may contribute to the sustained increase of intracranial pressure observed during prolonged anesthesia with enflurane. In contrast, the different alterations of CSF dynamics caused by isoflurane, namely decrease of Rawith no change in Vss, may explain, in part, why minimal increase of intracranial pressure is observed during prolonged anesthesia with isoflurane. Because decreased Rsimproves spatial compensation by cerebrospinal fluid volume for increased intracranial pressure, isoflurane may offer an advantage over enflurane in patients at risk because of increased intracranial pressure.