Despite the fact that dengue is a major disease affecting the tropical world, little is known of its pathogenesis due, partly, to the lack of a suitable animal model and the complex cell interactions in infected individuals. Using microarray analysis of gene expression and high throughput quantitative real-time PCR, we investigated the host response to dengue infection in cell lines and in DF patients. We further validated our microarray results by functional study of the identified genes. Although dendritic cells, Langerhans cells and monocytes have been proposed as the principle reservoirs of viral infection [4] , it is not clear which other tissues, if any, are targeted. Immunohistochemistry and in-situ hybridisation studies of biopsies from DHF patients have indicated that a range of tissues are infected by the virus, including cells in the liver, spleen, lung, kidney and peripheral blood [5] . We chose the HepG2 cell line as the primary cell model for this study as it readily supported viral replication, and it is derived from the liver, which might be of some clinical relevance. The A549 cell line was included as it was also an excellent supporter of viral replication even though there is, presumably, little or no clinical relevance. The final clinical relevance came from the validation of the genes in 10 DF patients from the Singapore EDEN cohort. The 10 patients were selected based on low platelet count, because of the lack of WHO DHF/DSS manifestation in Singapore adult patients. Despite the limited sample number, and the wide range of collection times, variation between individuals at the same time point was ruled out by statistical analysis. We believe that with more patients, more genes that are differentially expressed would be identified.