BACKGROUND: DNA microarrays technology has been used to obtain expression profiles of thousands of genes at the same time for a given organism at relatively low costs. While gene expression approaches are being developed which allow holistic analysis of complex biological processes, there exist very few illustrative examples on the integration of large scale modeling and high throughput time course experiments to upgrade the information contents on yeast biology. RESULTS: Saccharomyces cerevisiae cell culture experiments with perturbed growth conditions were designed so that the metabolic states would be shifted from one to another. Microarrays were used to explore changes in gene expression across the entire yeast genome during the perturbation experiments. Changes in transcript abundance in these growth periods were investigated to study the cellular response to different glucose and oxygen supply. Computational results and experimental observations representing the three characteristic metabolic states were compared on the S. cerevisiae metabolic pathways, as well as the visualization platform provided by the metabolic phenotypic phase plane (PhPP) for the gene regulation on cell metabolism and adaptation of cells to environmental changes. CONCLUSIONS: The integrated expression study described reveals that S. cerevisiae cells respond to environmental changes mainly by down-regulating a number of genes to alter the cell metabolism so that the cells adapt to the variations in their growth conditions. (C) 2009 Society of Chemical Industry