In many plant–pathogen interactions resistance to disease is controlled by the interaction of plant–encoded resistance (R) genes and pathogen–encoded avirulence (Avr) genes. The interaction between tomato and the leaf mould pathogen Cladosporium fulvum is an ideal system to study the molecular basis of pathogen perception by plants. A total of four tomato genes for resistance to C. fulvum (Cf–2, Cf–4, Cf–5 and Cf–9) have been isolated from two genetically complex chromosomal loci. Their gene products recognize specific C. fulvum–encoded avirulence gene products (Avr2, Avr4, Avr5 and Avr9) by an unknown molecular mechanism. Cf genes encode extracellular membrane–anchored glycoproteins comprised predominantly of 24 amino acid leucine–rich repeats (LRRs). Cf genes from the same locus encode proteins which are more than 90% identical. Most of the amino–acid sequence differences correspond to the solvent–exposed residues within a β–strand/β–turn structural motif which is highly conserved in LRR proteins. Sequence variability within this motif is predicted to affect the specificity of ligand binding. Our analysis of Cf gene loci at the molecular level has shown they comprise tandemly duplicated homologous genes, and suggests a molecular mechanism for the generation of sequence diversity at these loci. Our analysis provides further insight into the molecular basis of pathogen perception by plants and the organization and evolution of R gene loci.