Unexplained syncope may cause diagnostic and therapeutic problems in children. The head-up tilt test has been shown to be a useful tool for investigating unexplained syncope, especially for diagnosis of neurally mediated syncope. In this study 20 patients aged 9-18 years (12.0 +/- 2.5 years) with syncope of unknown origin and 10 healthy age-matched children were evaluated by head-up tilt to 60 degrees for 25 minutes. The test was considered positive if syncope or presyncope developed in association with hypotension, bradycardia, or both. If tilting alone did not induce symptoms (syncope or presyncope), isoproterenol infusion was administered with increasing doses (0.02-0.08 mu g/kg per minute). During the tilt test, symptoms were elicited in 15 (75%) of the patients with unexplained syncope but in only one (10%) of the control group (p < 0.001), The sensitivity of the test was 75% and its specificity 90%. Three patterns of response to upright tilt were observed in symptomatic patients: vasodepressor pattern with an abrupt fall in blood pressure in 67%; cardioinhibitory pattern with profound bradycardia in 6%; and mixed pattern in 27%. In patients with positive head-up tilt, there were sudden decreases in systolic blood pressure (from 130 +/- 15 to 61 +/- 33 mmHg) and in mean heart rate (from 147 +/- 26 to 90 +/- 38 beats per minute) (p < 0.001) during symptoms. Treatments with atenolol 25 mg/day has shown complete suppression of syncope in positive responders during a mean follow-up period of 18 +/- 6 months. The head-up tilt test is a noninvasive, sensitive, specific diagnostic tool for evaluating children with unexplained syncope.