HOST genotype specificity in interactions between biotrophic pathogens and plants in most cases complies with the gene-for-gene model1; success or failure of infection is determined by absence or presence of complementary genes, avirulence and resistance genes, in the pathogen and host plant, respectively. Resistance, expressed by the induction of a hypersensitive response in the host, is envisaged to be based on recognition of the pathogen, mediated through direct interaction between products of pathogen avirulence genes (the so-called race-specific elicitors) and receptors in the host plant, the putative products of resistance genes1. The interaction between the biotrophic fungus Cladosporium fulvum and its only host, tomato (Lycopersicon esculentum), is a well-established model system for studying fungus-plant gene-for-gene relationships1. Here we report the isolation of race-specific elicitor AVR4 of C. fulvum and the cloning of its encoding avirulence gene. We present evidence that, in nature, a single base-pair change in this avirulence gene leads to virulence of races previously avirulent on tomato genotypes carrying the complementary Cf4 resistance gene.