The cerebral haemodynamic effects of vasodilators are of clinical interest because a decrease in mean arterial pressure (MAP) might alter global cerebral blood flow (CBF). Luxury perfusion of the brain, contrast, might be unfavourable in patients with reduced intracranial compliance. Despite the widespread use of nitroglycerine (NTG), little is known about the cerebral haemodynamic consequence of NTG infusions in humans. This prospective, controlled study was designed: (1) to investigate the effects of NTG on CBF and cerebrovascular CO2 reactivity and (2) to compare reference measurements of global CBF with transcranial Doppler monitoring (TCD) of middle cerebral artery flow velocity (VMCA). METHODS With ethical committee approval and informed patient consent, we investigated ten patients undergoing coronary artery bypass surgery. Measurements were performed under fentanyl/midazolam anaesthesia prior to the start of the operation. First, during a baseline period, ventilation was changed in a random sequence to achieve two different levels of arterial PCO2 (30 and 50 mmHg, respectively). Consequently, measurements were repeated during i.v. infusion of 1.5.micrograms.kg-1.min-1 NTG at identifical PCO2 levels. Measurements of CBF were performed by the Kety-Schmidt technique with argon as an indicator. Simultaneously, VMCA was recorded by use of a 2-Mhz transcranial Doppler system. Cerebral perfusion pressure (CPP) was calculated from the difference between MAP and jugular bulb pressure. Statistical analysis was performed by two-way analysis of variance using a repeated-measures design to assess the effects of NTG application and respiratory changes, respectively. RESULTS During NTG infusion, CPP decreased slightly by 15-17%. Because of a reduction in cerebrovascular resistance, CBF increased at both levels of PaCO2 by 96 and 69%, respectively. However, VMCA decreased concomitantly. Cerebrovascular CO2 reactivity did not change. CONCLUSIONS This study demonstrates that during fentanyl/midazolam anaesthesia NTG may cause a major increase in CBF as long as CPP does not decrease considerably. Our results further suggest that NTG causes vasodilation of basal cerebral arteries, inducing a discrepancy between relative changes in CBF and VMCA. Consequently, TCD measurements during infusion of NTG should not be directly compared with preceding measurements of MCA flow velocity.