Technical Abstract: Among the most important diseases of soybean worldwide is the disease called Sudden Death Syndrome (SDS) caused by Fusarium virguliforme. This soil-borne fungus colonizes soybean roots causing root rot, and also releases a phytotoxin that is translocated to leaves causing interveinal chlorosis and necrosis leading to the symptoms of scorching and possible defoliation. Here we report on a gene expression study investigating the early response of soybean leaves to the phytotoxin present in sterile filtrates of F. virguliforme cultures (Fv toxin). Cross comparison of the gene expression profiles from different genotypes with different levels of resistance to Fv toxin allowed identification of some SDS related defense genes that were induced specifically in the more resistant genotype. Further functional annotations based on sequence homology suggested that some of the induced genes might encode proteins involved in cell-wall modification, detoxification, defense responses, primary metabolism and membrane transport. Quantitative real-time reverse-transcribed PCR confirmed the differential transcript accumulation of a subset of these genes. Additionally, in silico mapping of differentially expressed genes to SDS resistant quantitative trait loci (QTL), allowed for identification of new potential resistance molecular markers that can be genetically mapped to the soybean genome and could be further used in a maker assistant selection (MAS) program. Comparison of soybean response to Fv phytotoxin with other biotic and abiotic stresses revealed that the resistance response to Fv phytotoxin is quite similar to the response to inoculation with an incompatible Pseudomonas syringae pv. glycinae (Psg) strain, suggesting that Fv toxin might induce hypersensitive response pathways in soybean leaf tissues, in the absence of pathogen in these tissues.