The American Beech (Fagus grandifolia) is a hardwood tree found in the eastern half of North America and it is a vital source of high quality hardwood for furniture and other wood products. This important forest tree is currently susceptible to the Beech bark disease (BBD), which is causing considerable mortality. To gain insights into the molecular mechanisms underlying disease resistance in F. grandifolia RNA samples were sequenced using Roche 454 sequencing technology. RNA was isolated from both disease resistant and disease-susceptible trees which were identified in natural forest stands and are part of the US Forest Service BBD resistance genetic improvement program. In this study, we have identified preliminary gene networks for response of the American beech to BBD. This involves candidate gene identification by comparisons to orthologues in Arabidopsis and poplar model plant systems. According to their differential gene expression levels, candidate genes have been selected for functional studies from the networks. In the future, we will establish a database of gene networks for insect, disease, pathogen infection and tissue specific expression patterns. Finally, we intend to use the gene sequence resources to construct genetic linkage maps and for marker-assisted selection to develop tolerance to BBD in American beech. This project is supported by grant STDP #09-CA-11242304-100 from the U.S.D.A. Forest Service Special TechnologyDevelopment Program.