Abstract Motivation: In determining the function of a gene, it provides much information to observe the changes in a biological system after disruption of the gene of interest through its knockout. Thanks to the microarray technology, it is now possible to profile transcriptional changes of the whole genome, thus differentiating genes that are significantly affected by the knockout. Based on microarray experiments of hundreds of different knockouts, we assigned the so called, ‘Perturbation Sensitivity’, to the Saccharomyces cerevisiae genome by the frequency of significant changes in the transcript level in hundreds of knockout conditions. Biologically, it reflects the degree of a gene's sensitivity to external perturbations. Results: Through gradually enriching gene sets with more perturbation sensitive genes, we show that perturbation sensitive genes are usually not essential and their coding proteins have fewer physical interaction partners and more transcription factors bind to their upstream sequences. And the two extreme gene groups, perturbation sensitive versus perturbation resistant, have mutually exclusive functional annotations. contact: juhan@snu.ac.kr