The hypothalamic-pituitary axis (HPA) may be involved early in multiple system atrophy (MSA), whereas in idiopathic Parkinson's disease (IPD) its impairment seems to be correlated with motor disability. The release of prolactin (PRL) is mediated through the HPA and an increase in PRL levels is documented during stress. In this study, we investigated basal and erect PRL levels to assess whether basal PRL or changes in PRL levels after 60 degrees head-up tilt (HUT; orthostatic stress) could distinguish between MSA and IPD patients. We studied five patients with MSA on levodopa treatment, five levodopa-naive MSA patients, nine IPD patients on dopaminergic treatment, six drug-naive IPD patients and six normal individuals. PRL levels were measured in the supine position after 30 minutes rest and during 60 degrees HUT after 5 and 15 minutes. Baseline PRL values were significantly lower for patients with IPD than for those with MSA, both for levodopa-treated and naive patients ( p < 0.004, estimated decrease 55.1 %, 95 % CI from 29.4 % to 71.52 %). After orthostatic stress PRL levels were increased in healthy individuals after 15 minutes of HUT ( p = 0.044, estimated increase 11.5 %, 95 % CI from 0.4 % to 23.8 %), whereas there was no evidence for a change of PRL levels in patients with MSA or IPD after 5 and 15 minutes of HUT. We also did not find any evidence for a difference in PRL change after HUT between MSA and IPD patients. Baseline PRL levels might differentiate between early MSA and IPD, being higher in MSA. However, orthostatic stress using HUT appears unable to differentiate between MSA and IPD.