BACKGROUND: Simultaneous recordings of arterial blood pressure (ABP) and middle cerebral artery blood velocity can be used to calculate the apparent zero flow pressure (aZFP). The inverse of the slope of the pressure-velocity relationship is known as resistance area product (RAP) and is an index of cerebrovascular resistance. There is little information available regarding the effects of vasoactive drugs, arterial carbon dioxide (Paco2), and impaired cerebral autoregulation on aZFP and RAP during general anesthesia. During isoflurane anesthesia, we investigated the effects of hypocapnia and the effects of a phenylephrine infusion, on aZFP and RAP. METHODS: Radial ABP and transcranial Doppler middle cerebral artery blood velocity signals were recorded in 11 adults undergoing isoflurane anesthesia. A phenylephrine infusion was used to increase ABP and ventilation was adjusted to control Paco2. Cerebral hemodynamic variables were compared at two levels of mean ABP (approximately 80 and 100 mm Hg) and at two levels of Paco2: normocapnia (Paco2 38-43 mm Hg) and hypocapnia (Paco2 27-34 mm Hg). Two aZFP analysis methods were compared: one based on linear regression and one based on Fourier analysis of the waveforms. RESULTS: At the lower ABP, aZFP was 23 ± 11 mm Hg and 30 ± 13 mm Hg (mean ± sd) with normocapnia and hypocapnia, respectively (P < 0.001) and RAP was 0.76 ± 0.97 mm Hg • s • cm and 1.16 ± 0.16 mm Hg • s • cm with normocapnia and hypocapnia, respectively (P < 0.001). Similar effects of hypocapnia were seen at the higher ABP. With normocapnia, isoflurane impaired cerebral autoregulation and aZFP did not change with the increase in ABP. With hypocapnia, cerebral autoregulation was not significantly impaired and increasing ABP was associated with increased aZFP (from 30 ± 13 to 35 ± 13 mm Hg, P < 0.01) and increased RAP (from 1.16 ± 0.16 to 1.52 ± 0.20 mm Hg • s • cm, P < 0.001). Calculation of the relative contributions of aZFP and RAP to the cerebral hemodynamic responses indicated that changes in RAP appeared to have a greater influence than changes in aZFP. The mean difference between the two methods of determining aZFP (Fourier-regression) was 0.5 ± 3.6 mm Hg (mean ± 2sd). CONCLUSIONS: During isoflurane anesthesia, two interventions that increase cerebral arteriolar tone, hypocapnia and the autoregulatory response to increasing ABP, were associated with increased RAP and increased aZFP. The effect of changes in RAP appeared to be quantitatively greater than the effects of changes in aZFP. These results imply that arteriolar tone influences cerebral blood flow by controlling both resistance and effective downstream pressure.