The reduction in cerebral blood flow (CBF) caused by hypocapnia is an important element of neuroanesthetic techniques. While it has been demonstrated previously that the CO2 response of the cerebral circulation (CO2.R) is enhanced (i.e., greater ΔCBF/ΔPa(CO2)) during halothane administration, the effect of isoflurane on CO2.R has not been evaluated completely. Accordingly, the authors examined CO2.R in cats during anesthesia with 1.0 MAC isoflurane (with 75% N2O) and compared it with CO2.R during anesthesia with 1.0 MAC halothane (with 75% N2O) and with CO2.R during the administration of 75% N2O alone. CO2.R during anesthesia with isoflurane-N2O was enhanced relative to that observed during administration of both halothane-N2O (P < 0.025) and N2O alone (P < .001). CO2.R during anesthesia with halothane-N2O was, in turn, greater than that observed during the administration of N2O alone (P < 0.025). Furthermore, at similar levels of hypocapnia (Pa(CO2) 18-20 mmHg), CBF was significantly lower (P < 0.01) during administration of isoflurane-N2O (29.0 ± 4.5 ml.100 g-1.min-1) than during administration of either N2O (40.6 ± 5.5 ml.100 g-1.min-1) or halothane-N2O (39.6 ± 7.8 ml.100 g-1.min-1). CBF values during administration of the N2O alone and halothane-N2O were not different during hypocapnia. The results of this study indicate that CO2.R in cats not only is preserved during administration of 1.0 MAC isoflurane (with 75% N2O) but is enhanced relative to that observed during anesthesia with 1.0 MAC halothane (with 75% N2O) and during sedation with N2O alone. In addition, the induction hypocapnia (Pa(CO2) 18-20 mmHg) resulted in a reduction of CBF to lower levels during the administration of isoflurane-N2O than during administration of halothane-N2O or N2O alone. If the cerebral circulation of anesthetized humans responds similarly to that of the cat, these results suggest that the induction of hypocapnia during the administration of isoflurane (with N2O) may facilitate a greater reduction in CBF, and therefore perhaps ICP, than will occur at a comparable Pa(CO2) during anesthesia with halothane (with N2O) or during the administration of N2O alone.