Streptococcus pneumoniae, is the primary cause of invasive bacterial disease in children and the elderly. This organism infects the lung with devastating consequences. Worldwide, over 5 million children under the age of 5 die of S. pneumoniae-acquired pneumonia each year. S. pneumoniae is also responsible for more than 12 million cases of middle ear and sinus infections annually. Given its impact on public health, surprisingly few virulence determinants have been described, and little is known about how these factors are regulated in pneumococci. There is a growing body of evidence suggesting that the regulation of a number of virulence factors depends on the cell density of the pneumococci (Quorum Sensing; QS). Using microarray analysis, I will investigate, on a genome-wide scale, the role of QS regulation in S. pneumoniae pathogenicity under conditions of in vitro broth culture, in vitro cell culture, and ultimately in two pneumococcal animal models of infection. I hope the results of this approach will contribute to a much more comprehensive molecular description of S. pneumonia/host relationship and the diseases.