Resistance to bacterial speck disease in tomato occurs when the Pto kinase in the plant responds to expression of the avirulence gene avrPto in the Pseudomonas pathogen. Transient expression of an avrPto transgene in plant cells containing Pto elicited a defense response. In the yeast two-hybrid system, the Pto kinase physically interacted with AvrPto. Alterations of AvrPto or Pto that disrupted the interaction in yeast also abolished disease resistance in plants. The physical interaction of AvrPto and Pto provides an explanation of gene-for-gene specificity in bacterial speck disease resistance.