Previous research has indicated that in Parkinson's disease (PD) some motor speech characteristics are changed by levodopa administration, while others are not. In advanced PD, the time course of these changes and the correlations with motor performance have not been sufficiently investigated. The purpose was to investigate the sequential changes of respiratory, articulatory, and phonatory speech characteristics across a levodopa drug cycle, using spirometry, acoustic, and motor speech analysis. Seven patients with advanced PD were included. All patients were evaluated sequentually at 15 minute intervals before and following levodopa intake. Data were analysed using repeated measures ANOVA and non-parametric analysis. Significant changes were found in motor function, vital capacity, and standard deviation of the diadochokinetic period. A trend was present for shimmer and frequency of the first formant. Significant inter-individual differences in the sequential changes were demonstrated for nearly all evaluated parameters. The conclusion is that, in advanced PD, the evaluation of speech characteristics at one moment after levodopa administration is not representative of an entire drug cycle and that an individualized evaluation of an entire drug cycle is warranted before initiation of a speech-language pathology program.