Because of its mixed mating system and high potential gene flow, Melampsora larici-populina belongs to the group of pathogens with the highest evolutionary risk. Indeed, all qualitative resistances that have been selected by breeders during the last decades have been defeated. Although quantitative resistance (QR) is often considered more durable, a multidisciplinary approach is being conducted at INRA not only to identify the genes controlling QR but also to predict potential adaptation of the pathogen. Starting with a single Populus deltoides × P. trichocarpa F 1 pedigree, this work led to the identification of several QTLs with contrasted levels of effect and strain-specificity. Much attention is being paid to two major loci, R 1 and R US , that both map on LG XIX. Dominant allele R 1 is inherited from P. deltoides. It controls a qualitative resistance to M. larici-populina, and it was found to be statistically associated with QR levels in several P. deltoides × P. trichocarpa F 1 progenies. Dominant allele R US is inherited from P. trichocarpa. It has major effect of uredinia size and other QR components in both intraspecific and interspecific F 1 progenies. Fine mapping of R US is being conducted using a 1300 genotype F 1 host progeny, and a BAC library was constructed to generate a physical map of 2000 kb around R US . A promising BAC clone has been identified and sequenced. In parallel, an expressional approach based on the analysis of R US and r US infected material generated transcriptional and translational candidates. On the pathogen side, one strain was found to be able to circumvent R US , thus offering the opportunity to study the frequency and the mechanisms of adaptation to QR. Several populations of M. larici-populina that underwent contrasted selection pressures by R US are being characterized for their phenotypes and for their genotypes at several microsatellite loci. The first results demonstrate the existence of preadaptation in “wild” pathogen Populations and a clear selective pressure by the host.