Background: The responsiveness of a measurement instrument is important for understanding its ability to detect changes in the progression of a disease. We examined and compared the internal and external responsiveness of the 36-item Short-Form Health Survey (SF-36) and the 39-item Parkinson's Disease Questionnaire (PDQ-39) in patients with Parkinson's Disease (PD). Methods: Seventy-four patients with PD were evaluated using the SF-36 and PDQ-39 at baseline and again after one year. In addition, their motor signs, motor difficulties of daily living, and depressive symptoms were assessed as external criteria. The internal responsiveness was examined using effect size, standardized response mean, and the Wilcoxon signed rank test. The external responsiveness was examined using receiver operating characteristic curves, correlation analyses, and regression models. Results: Both instruments were partially sensitive to changes during the 1-year follow-up and able to discriminate between patients with improved versus deteriorated motor signs. In addition, both were similarly responsive to changes in the motor difficulties of daily living; the SF-36 appeared to be more sensitive than the PDQ-39 to changes in depressive symptoms. Conclusions: The SF-36 and the PDQ-39 were acceptably internally and externally responsive during the 1-year follow-up.