OBJECTIVE: The aim of this study was to determine the prevalence of autonomic dysfunction using the composite autonomic scoring scale (CASS) and heart rate variability (HRV) in patients with clinically isolated syndrome (CIS) and to correlate autonomic dysfunction with other measures of MS disease activity. METHODS: CASS, HRV and plasma catecholamines during supine and tilted phase were performed in 104 CIS patients. MRI findings were analyzed for total number of lesions and the presence of brainstem and cervical spinal cord lesions. RESULTS: Autonomic dysfunction (CASS >1) was present in 59.8 % of patients, parasympathetic dysfunction in 5 %, sympathetic in 42.6 % and sudomotor in 32.7 % of patients. Patients with autonomic dysfunction on CASS had lower level of norepinephrine in the supine position compared to patients without autonomic dysfunction (1.06 +/- 0.53 vs. 1.37 +/- 0.86, p = 0.048). The CASS score showed positive correlation with s-HF (r = 0.226, p = 0.031), s-SDNN (r = 0.221, p = 0.035), t-HF (r = 0.225, p = 0.032), and t-HFnu (r = 0.216, p = 0.04), and a negative correlation with t-LF/HF (r = -0.218, p = 0.038). More patients with MRI brainstem lesions had a positive adrenergic index (p = 0.038). Patients with MRI brainstem lesions also had a lower t-SDNN (26.2 +/- 14.2 vs. 32 +/- 13.3, p = 0.036) and a lower t-LF (median 415.0 vs. 575.5, p = 0.018) compared to patients without these lesions. Patients with adrenergic index >/=1 had a significantly higher standing heart rate compared to patients with an adrenergic index of 0 (96 +/- 13.5 vs. 90 +/- 12, p = 0.032). CONCLUSION: Autonomic (primarily sympathetic) dysfunction is present in a large proportion of early MS patients and it seems to be related to brainstem involvement.