Mutant screens have identified several genes in tomato, barley and Arabidopsis that are required for the function of specific plant disease resistance (R) genes. Two of these genes, NDR1 and EDS1, have recently been cloned from Arabidopsis. Most Arabidopsis R genes require NDR1 or EDS1, but not both. In a complementary approach, yeast two-hybrid screens have identified several proteins in tomato that interact with the Pto R gene protein, including a kinase and three putative transcription factors. The present data indicate that R gene proteins directly activate multiple signal transduction pathways, and that common defense responses can be activated via independent pathways.