The genetic nature of tree adaptation to drought stress was examined by utilising variation in the drought response of an F₂ mapping population from a cross between Populus trichocarpa (93-968) and P. deltoides Bart (ILL-129) known to be highly divergent for a vast range of phenotypic traits. Phenotyping, QTL analysis and microarray experiments were combined to demonstrate that "genetical genomics" can be used to provide information on adaptation at the species level. The grandparents and F₂ population were subjected to soil drying and contrasting responses to drought across genotypes including for leaf coloration, expansion, and abscission were observed and QTL for these traits were identified. A subset of extreme genotypes exhibiting extreme sensitivity and insensitivity to drought on the basis of abscission were defined and microarray experiments were conducted on these genotypes and the grandparents. The different groups induced a different set of genes; 215 and 125 genes differed in their expression response in control and drought respectively, suggesting species adaptation at the gene expression level. Genes preferentially expressed in drought resistance genotypes overlapped with genes expressed in dormant tissues whereas genes involved in meristem function had a lower expression. Co-location of differentially expressed genes with drought specific and drought responsive QTLs was identified and these represent candidate genes contributing to the variation in drought response.