BIBN4096BS is a CGRP-antagonist effective in the treatment of migraine. Blocking the receptor of a strong vasodilator involves a theoretical risk of causing cerebral vasoconstriction, a probability not previously investigated with BIBN4096BS. Seven healthy volunteers completed this double-blinded placebo-controlled crossover study. The volunteers received randomly 10 min infusions of either placebo, 2.5 mg or 10 mg of BIBN4096BS on 3 separate days. Transcranial Doppler was used to measure the middle cerebral artery blood flow velocity (VMCA); global and regional cerebral blood flow (rCBFMCA) was measured by 133-Xenon inhalation SPECT. The diameter of the temporal and radial artery was measured by high-resolution ultrasound. Systemic haemodynamics and partial pressure of CO2 (PetCO2), and adverse events were monitored regularly. BIBN4096BS had no influence on global or regional cerebral blood flow, or on the blood flow velocity in the middle cerebral artery. There was no effect on systemic haemodynamics and adverse events were minor. We conclude that there is no effect of CGRP-receptor blockade on the cerebral or systemic circulation in humans. Circulating CGRP is therefore not likely to exert a vasodilatory activity in the resting state and the use of BIBN4096BS for acute migraine seems to be without risk of cerebral vasoactivity. These data suggest that BIBN4096BS is the first specific antimigraine drug without vasoactive effect.