Head-up tilt testing has gained acceptance as a tool for assessing susceptibility to neurally mediated syncopal syndromes (e.g., vasovagal syncope), and is currently being evaluated as a means of testing therapeutic interventions in these conditions. To assess reproducibility of head-up tilt testing and thereby assess the potential of such testing for immediate evaluation of a planned treatment, findings during 2 sequential 80 ° headup tilt tests were compared in 23 patients (age range 6.5 to 74 years) undergoing evaluation of syncope of unknown origin. Upright tilt was performed initially in the absence of drugs, and repeated if necessary during pharmacologic provocation by means of isoproterenol infusions of 1 and 3 μg/min (tilt 1). End points were syncope, maximal tolerated isoproterenol dose, or a tilt duration of 10 minutes. The second tilt test (tilt 2) was conducted after approximately 30 minutes of supine rest using the maximal provocative conditions used in tilt 1. Fifteen of 23 patients (65%) developed syncope in either tilt l or 2, while 8 of 23 (35%) remained asymptomatic. Tilt testing results were concordant (i.e., positive in both tests, or negative in both tests) in 20 of 23 (87%) patients. Concordance was, however, less among tilt-positive patients (12 of 15, 80%) since 3 patients were tilt-positive in tilt 1 only. In the 15 tiltpositive patients, heart rates, systolic and diastolic blood pressures at time of maximal tilt provocation were similar for both tilts (heart rate 1, 67 ± 27; 2, 82 ± 34 beats/min; systolk blood pressure 1: 50 ± 11 mm Hg; 2, 60 ± 21 mm Hg [p = not significant (NS)]; diastolic Wood pressure 1, 27 ± 12 mm Hg; 2, 33 ± 18 mm Hg [p = NS]). Furthermore, time from tilt onset to syncope did not differ in tilt 1 and 2. Among the 15 patients who were tilt-positive in tilt 1, the procedure was tolerated for 3.7 ± 2.1 minutes during the first test compared with 4.5 ± 3.2 minutes in the second test (p = NS). The outcomes were even closer if only patients developing syncope during both tests are considered (tilt 1, 3.7 ± 2.1 minutes vs tilt 2, 3.1 ± 1.8 minutes). Similarly, in the 8 tilt-test negative patients, minimal recorded systolic blood pressure and diastolic blood pressure did not differ in the 2 tests. Thus, upright tilt testing appears to exhibit a relatively high degree of reproducibility when a second study is performed on the same day. Consequently, 2 sequential tilt tests may be useful for assessing the immediate effect of therapeutic interventions on susceptibility to neurally mediated hypotension-bradycardia syndrome.