Syncope is a common disorder that is potentially disabling and affects both young and old. Once neurological, cardiological, and metabolic causes have been excluded, there remains a group in which diagnosis is unclear; some may have an autonomic basis. We therefore did a retrospective study on consecutive patients referred to our tertiary referral autonomic centres between 1992 and 1998 with recurrent syncope and presyncope, in whom non-autonomic causes, before referral, had been sought and excluded. The object was to find out whether autonomic investigation helped diagnosis. Data from case notes and from the autonomic database on 641 patients were analysed. Syncopal patients with a known or provisional diagnosis of autonomic failure were excluded from analysis. The role of screening tests in establishing or excluding an autonomic cause was assessed. Response to additional autonomic tests (such as head-up tilt with or without venepuncture, and food challenge and exercise) was documented. Some patients underwent further testing if non-autonomic neurological, psychiatric, and other disorders were considered. Screening autonomic function tests indicated orthostatic hypotension and confirmed chronic autonomic failure in 31 (4.8%) patients. Neurally mediated syncope was diagnosed in 279 (43.5%) on the basis of clinical features and autonomic testing. Most had vasovagal syncope (227 [35%]); other causes included carotid sinus hypersensitivity (37 [5.8%]), and a group of 15 (2.3%) were associated with rarer causes such as micturition and swallowing. Miscellaneous cardiovascular causes (systemic hypotension, arrhythmias), or drugs, contributed to syncope in 53 (8.3%). Non-autonomic neurological causes included vestibular dysfunction (32 [5%]) and epilepsy (11 [1.7%]). In 56 (8.7%) a psychiatric cause was thought to be contributory. In 179 (27.9%), syncope was of unknown cause. In recurrent syncope and presyncope, when cardiac, neurological, and metabolic causes have been excluded, autonomic investigation can aid management by making, confirming, or excluding various factors or diagnoses.