Multiple system atrophy is distinguished from idiopathic Parkinson's disease by the arginine growth hormone stimulation test. Objective Multiple system atrophy (MSA) may be difficult to distinguish from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine growth hormone (GH) stimulation test in distinguishing between MSA and PD in large populations of patients. Methods We measured the GH response to arginine in 69 MSA (43 MSAp [parkinsonism as the main motor feature] and 26 MSAc [cerebellar features predominated]) patients, 35 PD patients, and 90 healthy control subjects. We used receiver-operating curve analysis to establish the arginine cutoff value that best differentiated between MSA and PD. Results The GH response to arginine was significantly lower (p < 0.01) in MSA than in either PD patients or control subjects. At a cutoff level of 4g/L, arginine distinguished MSAp from PD with a sensitivity and specificity of 91% and MSAc from PD with a sensitivity of 96% and specificity of 91%. The arginine test had a positive predictive value for MSA of 95%. The GH response to arginine was not affected by disease duration or severity, MSA motor subtype, pyramidal signs, response to dopaminergic therapy, or magnetic resonance imaging findings. Interpretation The GH response to arginine differentiates MSA from PD with a high diagnostic accuracy. The results suggest an impairment of cholinergic central systems modulating GH release in MSA. Ann Neurol 2006