Animal studies have demonstrated increases in sympathetic nerve outflow with vestibular stimulation. The purpose of the present study was to determine whether vestibulosympathetic reflexes are engaged in humans. Muscle sympathetic nerve activity (MSNA), heart rate, arterial pressure, calf blood flow (CBF), and calculated calf vascular resistance (CVR; mean arterial pressure/CBF) were determined during 10 min of baseline (laying prone with chin supported) and 10 min of head-down neck flexion (HDNF). MSNA responses were measured in nine subjects, and calf vascular responses were determined in seven of these subjects. Heart rate increased during the first minute of HDNF (71 +/- 2 to 76 +/- 3 beats/min; P < 0.05) and remained slightly elevated (71 +/- 2 to 74 +/- 3 beats/min; P < 0.05) for the duration of HDNF. Diastolic and mean arterial pressures also increased slightly with HDNF (80 +/- 3 to 82 +/- 3 and 96 +/- 3 to 98 +/- 3 mmHg, respectively; P < 0.05). Systolic arterial pressure did not change significantly during HDNF. CBF decreased 14% (4.63 +/- 0.78 to 3.97 +/- 0.60 ml x min(-1) x 100 ml(-1); P < 0.05), and CVR increased 12% (24.0 +/- 4.3 to 27.4 +/- 4.7 units; P < 0.05) during HDNF. These changes corresponded with significant increases in MSNA during HDNF. MSNA, expressed as burst frequency, increased from 14 +/- 2 to 20 +/- 2 bursts/min (P < 0.05) and increased 63 +/- 23% (P < 0.05) when expressed as the percent change in total activity. All variables returned to baseline during recovery. Thoracic impedance measured in five subjects did not change during HDNF (19.6 +/- 1.2 to 19.7 +/- 1.5 omega), suggesting no major change in central blood volume. The results indicate that HDNF elicits increases in CVR that are mediated by the augmentation of MSNA. Arterial pressure responses and thoracic impedance data suggest that high and low pressure baroreflexes were not the mechanism for sympathetic activation. The immediate increase in MSNA with HDNF suggests a role for vestibulosympathetic reflexes.