Two-dimensional echocardiography was performed during a head-up tilt test in 11 control subjects (group I) and 18 patients with recurrent unexplained syncope. In four patients (group II), the head-up tilt test was negative at baseline and after isoproterenol infusion. Syncope was induced during baseline head-up tilt in nine patients (group III) and after isoproterenol challenge in five (group IV). The echocardiographic variables assessed were left ventricular end-systolic and end-diastolic areas and percent fractional shortening. At the end of head-up tilt, end-systolic area decreased by 4.5 +/- 1.3 and 3.0 +/- 1.2 cm2 in groups III and IV, respectively, compared with 0.5 +/- 0.7 and 0.2 +/- 0.1 cm2 in groups I and II, respectively (p less than 0.04). Similarly, end-diastolic area decreased by 5.5 +/- 2.6 cm2 in group III compared with 2.7 +/- 1.9 and 1.75 +/- 0.4 cm2 in group I and II, respectively (p less than 0.04). Additionally, at the end of the baseline study, fractional shortening was significantly greater in group III and group IV (43 +/- 5%) than in groups I and II (p less than 0.01). In conclusion, syncope induced by head-up tilt is associated with vigorous myocardial contraction and a significant decrease in left ventricular end-systolic dimensions. This left ventricular hypercontractility may play an important role in the pathogenesis of syncope induced by head-up tilt.