The aim of the present study was to evaluate, through a case-control study, the specificity of the upright tilt test with bromocriptine as a marker of neurally mediated syncope of unknown aetiology. We have compared upright tilt test with bromocriptine (2.5 mg p.o.) in patients with syncope of unknown aetiology and controls. A total of 23 patients and controls matched by age and sex had upright tilt test with bromocriptine. The upright tilt test procedure consisted of 10 min in supine position, 10 min of 60 degree head-up tilt and a further 10 min with the subject supine; this procedure was performed in baseline condition and 60, 120, 180 and 240 min after the administration of bromocriptine. The protocol end points were the development of syncope or presyncope in association with hypotension with or without bradycardia. A positive response to bromocriptine test was found in 78% (95% CI, 61% to 95%) of patients and in 13% (95% CI, 0% to 26%) of controls (P<0.001). No significant differences were detectable among patients and controls showing a positive response to the test. Bromocriptine test seems to be a useful alternative tool for the diagnosis of neuromediated syncope also suggesting that dopaminergic supersensitivity may, at various and to varying degrees, play a role in the pathogenesis of syncopal episodes.