The fungus Synchytrium endobioticum, the causal agent of potato wart disease, is subject to world-wide quarKantine regulations due to the production of persistent resting spores and lack of effective chemical control measures. The selection of Synchytrium-resistant potato cultivars may be facilitated by using markers closely linked with a resistance gene or by transferring a cloned gene for resistance into susceptible cultivars. Sen1, a gene for resistance to Synchytrium endobioticum race 1, was localized on potato chromosome XI in a genomic region which is related to the tobacco genome segment harbouring the N gene for resistance to TMV. Using N as probe, we isolated homologous cDNA clones from a Synchytrium-resistant potato line. The N-homologous sequences of potato identified by RFLP mapping a family of resistance gene-like sequences closely linked with the Sen1 locus. Sequence analysis of two full-length N-homologous cDNA clones revealed the presence of structural domains associated with resistance gene function. One clone (Nl-25) encodes a polypeptide of 61 kDa and harbours a Toll-interleukin like region (TIR) and a putative nucleotide binding site (NBS). The other clone (Nl-27) encodes a polypeptide of 95 kDa and harbours besides the TIR and NBS domains five imperfect leucine-rich repeats (LRRs). Both clones have at their amino terminus a conserved stretch of serine residues that was also found in the N gene, the RPP5 gene from Arabidopsis thaliana and several other resistance gene homologues, suggesting a function in the resistance response. Cloning of the disease resistance locus based on map position and the establishment of PCR-based marker assays to assist selection of wart resistant potato genotypes are discussed.