The influence of muscarinic blockade on the superior mesenteric artery (SMA) response to head-up tilt (HUT) was assessed by Doppler ultrasound in eight healthy adults pretreated with i.v. glycopyrron. During supine rest, cholinergic blockade increased heart rate from 58 +/- 3 to 106 +/- 6 beats min-1 (mean +/- SE) and mean arterial pressure from 81 +/- 3 to 97 +/- 4 mmHg (P < 0.01) and it reduced the cardiac stroke volume from 89 +/- 6 to 59 +/- 7 ml (P < 0.01) with no significant effect on the SMA diameter and blood flow velocities. HUT provoked a further increase in heart rate to 134 +/- 5 beats min-1 (P < 0.01) and a reduction in stroke volume to 45 +/- 4 ml (P < 0.01). The early diastolic velocity increased from -51 +/- 4 to 6 +/- 8 cm s-1 during the normotensive stage of HUT and further to 21 +/- 9 cm s-1 during the hypotensive stage with a reduction in mean arterial pressure from 97 +/- 4 to 73 +/- 7 mmHg (P < 0.01) but, in contrast to control HUT (without cholinergic blockade), the end-diastolic velocity did not change significantly. Maintenance of blood velocity and diameter in spite of an increase in arterial pressure at rest indicates increased SMA impedance. Likewise, during hypovolaemia, a glycopyrron-induced inhibition in diastolic velocity supports an increase in SMA impedance. The results indicate cholinergic vasorelaxing influence on the superior mesenteric artery both at rest and during normotensive central hypovolaemia.