To determine the usefulness of prolonged head-up tilt in the diagnosis of neurally mediated syncope, 201 patients with history of syncope of unknown cause and 102 age and gender matched control subjects underwent a 40 minute 60 degrees head-up tilt test. Head-up tilt elicited syncope (i.e., was positive) in 74 of the 201 patients (37%) with a history of unexplained syncope and in only 6 of the 102 controls (6%). The specificity of the test was 100% in patients 60 years of age and older. Symptoms during tilt-induced syncope were identified by the patients as similar to those they had suffered during their spontaneous episodes. All 80 subjects who had tilt-induced syncope recovered without sequelae. The positive predictive value of a positive responses to head-up tilt was 93% and the negative predictive value was 43%. The results indicate that the prolonged head-up tilt test is a very specific procedure of high diagnostic value in patients with a history of unexplained syncope. It is particularly useful in the elderly age groups who have a high incidence of syncope.