Central hypovolaemia induced by head-up tilt evokes a reduction in superior mesenteric artery resistance resulting in maintenance of regional blood flow. Mechanisms of importance for this response are not known, but a parasympathetic contribution could be expected. To evaluate this hypothesis, superior mesenteric artery blood flow and resistance were evaluated by duplex ultrasound in eight healthy volunteers during postprandial head-up tilt with and without cholinergic blockade. During supine rest, cholinergic blockade did not influence the postprandial reduction in peripheral mesenteric artery resistance as expressed by analogous elevations in the diastolic blood velocity (to 62 +/- 9 vs. 56 +/- 7 cm s-1 with placebo). Throughout the normotensive and hypotensive phases of head-up tilt, cholinergic blockade reduced mesenteric artery mean blood velocity by 39 and 42%, respectively, corresponding to volume flow reductions by 35 and 41% (0.62 +/- 0.10 vs. 0.96 +/- 0.13 L min-1 and 0.52 +/- 0.07 vs. 0.88 +/- 0.16 L min-1; P <0.05). Also, during both phases of head-up tilt, cholinergic blockade increased mesenteric artery resistance as reflected in a reduction in the diastolic blood velocity by 41 and 56%, respectively (44 +/- 4 vs. 74 +/- 13 cm s-1 and 24 +/- 6 vs. 54 +/- 8 cm s-1). These results support a cholinergic contribution to the mesenteric artery vasorelaxing response to central hypovolaemia induced by head-up tilt.