Cardiovascular autonomic functions were investigated in a prospective, controlled study of 22 consecutive relapsing-remitting multiple sclerosis (MS) patients and 22 healthy subjects using 5 simple noninvasive tests and sympathetic skin response testing. Tests included the heart rate response to deep breathing, valsalva maneuver and standing, blood pressure response to standing and sustained hand grip, and were graded according to the Ewing and Clark classification as early, definite or severe impairment. The relationship between autonomic dysfunction and disease-related parameters such as the expanded disability status scale (EDSS) and disease duration was studied. Ninety percent of the patients had symptoms related with autonomic dysfunction, and 45.5 % had abnormal results in cardiovascular autonomic function testing with 4 patients also having abnormal sympathetic skin responses. Statistical analysis indicated that patients with a long disease duration rather than high EDSS carried a risk of autonomic involvement in MS. Both parasympathetic and sympathetic functions were impaired and this could have been easily overlooked by a standard EDSS follow-up. In this regard, autonomic function testing seems necessary in order to detect subclinical changes in MS patients and should be considered in outcome measures.