This investigation tested the importance of excitatory amino acids' effects on regional cerebral O2 consumption and the concomitant changes in cerebral blood flow (rCBF) in isoflurane anesthetized rats. In the glutamate or N-methyl-D-aspartate (NMDA) groups, 10(-2) M glutamate or NMDA was topically applied to the right cortex and the left cortex was used as a control. One mg/kg dizocilpine maleate (MK-801), a non-competitive NMDA receptor antagonist, was administered (iv) to the MK-801 group and saline was given to the control group. Cortical rCBF was determined using 14C-iodoantipyrine and regional O2 extraction was measured microspectrophotometrically. Cerebral O2 consumption increased 77% after glutamate (contralateral cortex: 9.0 +/- 1.1 ml O2/min/100 g, glutamate treated cortex: 15.9 +/- 3.9), while a 46% increase was observed with the same concentration of NMDA (contralateral cortex: 9.8 +/- 2.0, NMDA treated cortex: 14.3 +/- 5.5). After MK-801, the O2 consumption decreased to 37% of the control value (control cortex: 7.0 +/- 1.3, MK-801 treated cortex: 2.6 +/- 3.9). MK-801 significantly decreased cerebral O2 extraction from 7.1 +/- 1.3 ml O2/100 ml (control cortex) to 5.3 +/- 0.6 (MK-801 treated cortex). However, there was no significant difference in cerebral O2 extraction between treated and contralateral cortex in either the glutamate or NMDA groups. The increase in O2 consumption caused by glutamate or NMDA was coupled with increased rCBF. Glutamate increased rCBF from 95 +/- 5 ml/min/100 g (contralateral cortex) to 165 +/- 31 (treated cortex), while NMDA increased rCBF from 114 +/- 12 (contralateral cortex) to 178 +/- 60 (treated cortex). MK-801 decreased O2 consumption with a lesser decrease of rCBF. The rCBF was 48 +/- 9 in the MK-801 treated cortex and 99 +/- 22 in the control cortex. Some substances produced by the activation of NMDA receptors may be related to the coupling of cerebral metabolism and blood flow, since after blockade of NMDA receptors with MK-801, this relationship is uncoupled. These findings suggest that glutamatergic processes have a major effect on cerebral O2 consumption and that this is at least partly due to NMDA receptors.