The head-up tilt test has demonstrated to be useful in the study of patients with syncope of unknown origin for the diagnosis of neurocardiogenic syncope. Several publications have described different methods, with different results in cases as well as in controls. We performed a prospective study in a group of normal subjects in order to evaluate the methodology used in our population and to establish its specificity. A positive test was defined as the presence of syncope or presyncope and hypotension. The examination was carried out on a tilt table, five minutes at 0 degree, then at 70 degrees during 20 min. In the absence of syncope or presyncope an i.v. infusion of isoproterenol was started afterwards in order to increase the heart rate 30-50% over the baseline values and administered during 20 min at 70 degrees. Twenty one volunteers (14 male and 7 women; mean age 26.7 +/- 3.5 years; range: 21-33 years) and body mass index 23.4 +/- 2.2 kg/m2 were examined. Mean dose of isoproterenol was 3.1 +/- 0.9 micrograms/min (3.4 +/- 1.1 in men and 2.6 +/- 0.7 micrograms/min in women, NS). During the phase without isoproterenol no subject developed hemodynamic alterations neither symptoms. One volunteer (4.8%) developed presyncope and systemic hypotension (52/28 mm Hg) accompanied with nodal rhythm after 14 min of isoproterenol at 70 degrees, and his examination was discontinued, with immediate recovery. Three other subjects developed asymptomatic transient nodal rhythm during the phase with isoproterenol and recovered spontaneously. No other complications were observed. It is concluded that head-up tilt test with isoproterenol at 70 degrees, with the used doses and heart rate increments, is highly specific (95%) to establish the diagnosis of a neurocardiogenic syncope.