To compare the cerebral vascular and metabolic effect of an isoflurane-nitrous oxide mixture to an equipotent dose of isoflurane at 1.1 minimum alveolar anesthetic concentration (MAC), and to study the interaction between nitrous oxide and isoflurane anesthesia, we measured right middle cerebral artery blood flow velocity (V mca) and cerebral arteriovenous oxygen content difference (AVDO2) in six healthy patients during normocapnia and normothermia under the following sequence of steady-state anesthetic conditions: Condition A, 0.5 MAC of isoflurane, Condition B, 0.5 MAC of isoflurane + 0.6 MAC of N2O, Condition C, 1.1 MAC of isoflurane + 0.6 MAC of N2O, and Condition D, 1.1 MAC of isoflurane. The study entry sequence was randomized. V mca and AVDO2 during 1.1 MAC of isoflurane (Condition D) was 48 +/- 7 cm/s and 3.9 +/- 0.6 vol%, respectively. Substituting 0.6 MAC of isoflurane with an equipotent concentration of N2O (Condition B) resulted in an increase in both V mca and AVDO2 of approximately 20% (P < 0.05). These findings suggest that the increase in flow was accompanied by an even greater increase in metabolic rate. Adding 0.6 MAC of N2O to 1.1 MAC of isoflurane (Condition C) also increased V mca (P < 0.05). We conclude that N2O is a more potent cerebral vasodilator than an equipotent dose of isoflurane alone in humans.