Aims Hevea brasiliensis cultivation is nearly the only source of production of natural rubber (latex), an irreplaceable strategic biopolymer for various industrial sectors. Worldwide production is threatened by the South American Leaf Blight (SALB) due to the fungus Microcyclus ulei (Ascomycota). CIRAD and Michelin collaborate, since 1992, on a program (CMB, Cirad-Michelin-Brésil) aiming at the creation of new varieties (grafted clones), combining high latex yield and tolerance to SALB. The ultimate objective is both to allow rubber farming development in the American inter-tropical zone endemically affected by the disease, and to prevent the risk of accidental introduction of the pathogen in the current Asian and African producing regions. The aim of the GENESALB project was to reinforce genetic mapping and candidate genes identification in order to speed up the characterization of genetics factors governing natural resistance to SALB and, ultimately, to set up a marker-aided selection program. Our strategy was based on the analysis of 6 mapping populations issued from 4 diversified tolerant progenitors, evaluated for SALB resistance in 2 locations (Brazil and/or French Guiana) in order to assess genetic diversity of resistance factors (major genes/loci and QTLs). Results Our results show that SALB resistance is mainly governed by major resistance genes/loci and each of the cultivar analyzed by genetic mapping led to the identification of a specific major resistance gene. These original results constitute a favorable context for a marker-aided selection of cultivars combining high yield and high level of SALB tolerance. In addition, it illustrates the richness of wild Amazonian genetic resources and their usefulness for disease resistance improvement in rubber tree. The project produced molecular resources for expression studies and breeding: cloning and sequencing of 6958 expressed genes associated with the disease, characterization of 489 candidate genes and set