Immediate responses to head-up tilt were determined in 78 consecutive patients with unexplained syncope undergoing 45-minute tilt tests at 60 degrees. Thirty-four patients developed neurally mediated syncope (mean time to syncope 18 minutes), 40 tolerated the full duration of tilt, and 4 were unable to complete the study but did not develop syncope. Blood pressure, heart rate, forearm blood flow and forearm vascular resistance were measured at baseline and after 2 and 5 minutes of tilt. Syncopal and nonsyncopal patients were well-matched for age and baseline hemodynamic parameters. There was no difference between the groups in heart rate or blood pressure at 2 minutes, but there was a small but significant difference in percent reduction in mean arterial pressure at 5 minutes. After 2 and 5 minutes of tilt, mean forearm blood flow was 2.4 and 2.6 ml/min/100 ml, respectively, in syncopal patients compared with 1.6 (p < 0.05) and 1.7 ml/min/100 ml (p < 0.01), respectively, in patients who tolerated 45 minutes of tilt. In syncopal patients, forearm vascular resistance was 51.0 and 44.0 at 2 and 5 minutes, respectively, whereas in nonsyncopal patients, it was 82.4 (p < 0.02) and 73.1 (p < 0.001), respectively. These differences remained consistent when only data for patients developing syncope after > 15 minutes were included in the analysis. Patients with neurally mediated syncope have clearly demonstrable abnormalities in vascular control immediately after assumption of the upright posture. The results shed new light on the pathophysiology of neurally mediated syncope.