Arteriovenous malformations (AVM's) are congenital tangles of vessels that have a high blood flow through a low-resistance nidus. The vessels in the nidus may lack normal vasoreactivity in response to changes in PaCO2 or perfusion pressure (autoregulation). Arteriovenous malformation hemodynamics have been assessed based on the response of AVM feeding arteries to hypocapnia. Twenty-five AVM patients, aged 34 +/- 11 years (mean +/- standard deviation), were admitted to the Massachusetts General Hospital for proton-beam radiation therapy. Fourteen healthy volunteers aged 30 +/- 7 years served as control subjects. Angiograms with calibrated markers permitting magnification correction were available for all patients. The limits of the middle cerebral artery, as determined by transcranial Doppler ultrasonography, were compared to measurements made on the angiograms. Hyperventilation was induced at a rate set by a metronome. Fixed bilateral Doppler probes allowed almost simultaneous sampling of two vessels. Volunteer control subjects were hyperventilated in two steps. The two PaCO2 step decreases were significant (mean resting PaCO2 40.6 +/- 3.5 mm Hg, Step 1 level 29.4 +/- 3.5 mm Hg and Step 2 level 23.8 +/- 3.5 mm Hg; p < 0.01). These decreases induced a significant decrease in mean flow velocity (Vm) and an increase in the pulsatility index (p < 0.001). Mean carbon dioxide reactivity (% delta Vm/delta PaCO2) was 2.74 +/- 1.0 for Step 1 and 1.44 +/- 1.8 for Step 2 (p < 0.003). The mean PaCO2 decrease in patients was from 39.5 +/- 4.0 mm Hg to 27.0 +/- 3.5 mm Hg. Carbon dioxide reactivity was 0.92 +/- 1.12 for feeding vessels and 2.59 +/- 1.78 for nonfeeding vessels (p < 0.001). Transcranial Doppler ultrasound and angiographic depth measurements correlated well. Hyperventilation induced significantly more hemodynamic changes in control and nonfeeding middle cerebral arteries than in feeding vessels. Impaired CO2 reactivity may help to identify AVM feeding vessels as well as the relative magnitude of the flow provided to the malformation.