Despite the initial reports showing beneficial effects of dopaminergic treatment on speech in Parkinson's disease (PD), more recent studies based upon valid measurements have not approved any improvement of speech performance under pharmacotherapy. The aim of this study was to analyze the effect of treatment initiation on the progression of speech impairment in PD, using novel evaluation criteria. Nineteen de novo patients with PD were tested and retested within 2 years after the introduction of antiparkinsonian therapy. As controls, 19 age-matched individuals were recorded. Speech examination included sustained phonation, fast syllable repetition, reading text, and monolog. Quantitative acoustic analyses of the key aspects of speech based on Gaussian kernel distribution, statistical decision-making theory, and healthy speech observation were used to assess the improvement or deterioration of speech. A trend for speech performances to improve was demonstrated after treatment mainly in quality of voice, intensity variability, pitch variability, and articulation. The treatment-related improvement differed in various aspects of speech for individual PD patients. Improvements in vowel articulation and pitch variability correlated with treatment-related changes in bradykinesia and rigidity, whereas voice quality and loudness variability improved independently. Using a novel approach of acoustic analysis and advanced statistics, improvements in speech performance can be demonstrated in PD patients after the introduction of antiparkinsonian therapy. Moreover, changes in speech articulation and pitch variability appear to be related with dopaminergic responsiveness of bradykinesia and rigidity. Therefore, speech may be a valuable marker of disease progression and treatment efficacy in PD.