We compared autonomic function in patients with multiple system atrophy (MSA) or with idiopathic Parkinson's disease (IPD) by measuring sympathetic skin response (SSR) and R-R interval variability (RRIV). SSR was investigated in 26 patients (13 with MSA and 13 patients with IPD). RRIV during deep breathing, Valsalva maneuver, and on standing was investigated in 20 patients (nine with MSA and 11 with IPD). MSA and IPD patients had similar age, illness duration, and therapy. Abnormal SSR was more frequent in MSA (69%) than in IPD (7.7%; x2, 10.4; p < 0.002). RRIV during deep breathing and the Valsalva maneuver was lower in MSA than in IPD (p = 0.02). RRIV during standing up was not significantly different in IPD and MSA. These differences between MSA and IPD may be due to more severe and widespread autonomic disturbance in MSA, related to more severe neuropathologic involvement of the autonomic nervous system. SSR and RRIV may aid in the differential diagnosis of parkinsonism and help to exclude from clinical trials MSA patients clinically misdiagnosed as having IPD.