Plant disease susceptibility is determined by complex interactions between plant and pathogen factors, resulting in co-evolution of a host plant species and its adapted pathogen. Previously, there has been major scientific interest in plant resistance that counteracts pathogen attack. In contrast, mechanisms of plant susceptibility are poorly understood. The aim of this study was to identify genetic determinants of dominant susceptibility of Arabidopsis thaliana to the hemibiotrophic ascomycete Colletotrichum higginsianum. Two different approaches were used, both based on the hypothesis that if an essential host susceptibility factor is not present or not functional, the plant will not support infection by the fungus. In the first approach, a forward genetics screen was conducted to identify mutants that had lost susceptibility due to chemically induced mutations in essential host susceptibility factors. Screening of 207,000 EMS Arabidopsis mutants in highly susceptible genetic backgrounds identified 35 candidates with reduced susceptibility to C. higginsianum. However, the reduction was not sufficiently clear-cut to allow identification of the mutated locus through positional cloning. The C. higginsianum infection phenotypes of available downy mildew resistant (dmr) and powdery mildew resistant (pmr) mutants were also analysed. Loss of susceptibility to C. higginsianum by specific dmr and pmr mutant lines indicated that pathogens share some common mechanisms of disease development. In the second approach, analysis of 116 Arabidopsis accessions from diverse geographic origins revealed considerable natural variation in response to C. higginsianum inoculation. Different modes of inheritance of resistance were identified by crossing resistant accessions to the highly susceptible Ler-0 accession and following segregation, and by quantitative trait loci (QTL) analysis of recombinant inbred line (RIL) populations. It was assumed that accessions lacking an essential dominant susceptibility factor would show monogenic recessively inherited resistance. Alternatively, recessive resistance could be due to the presence of a recessive resistance (R) gene. To select for recessive resistance, accessions that had susceptible F1 progenies and F2 progenies segregating 3:1 (susceptible : resistant) were characterised further. A single recessive locus was shown to confer resistance in the accessions Ws-0, Gifu-2 and Can-0. The same locus was identified by QTL analysis in the Ler-0 x Kondara RIL population. Positional cloning in a Ler-0 x Ws-0 F2 mapping population located this recessive resistance locus to the lower arm of chromosome V between the molecular markers �236� (18,307,842 bp) and �312� (18,407,860 bp). Twenty candidate genes within the mapping interval, including six TIR (Toll-Interleukin 1 receptor) type NBS-LRR (Nucleotide Binding Site�Leucine Rich Repeats) genes, were analysed to determine whether this locus encodes a dominant susceptibility factor, or alternatively, a recessive R gene. Natural variation was also characterised cytologically. This revealed differences between resistant and susceptible accessions at an early stage in the penetration efficiency of the pathogen, or in the establishment of biotrophic primary hyphae, with no indications of involvement of host callose deposition or accumulation of reactive oxygen species in recessive resistance mechanisms.