To promote host colonization, many plant pathogens secrete effector proteins that either suppress or counteract host defences. However, when these effectors are recognized by the host's innate immune system, they trigger resistance rather than promoting virulence. Effectors are therefore key molecules in determining disease susceptibility or resistance. We show here that Avr2, secreted by the vascular wilt fungusFusarium oxysporumf. sp.lycopersici(Fol), shows both activities: it is required for full virulence in a susceptible host and also triggers resistance in tomato plants carrying the resistance geneI-2. Point mutations inAVR2, causing single amino acid changes, are associated withI-2-breakingFolstrains. These point mutations prevent recognition byI-2, both in tomato and when both genes are co-expressed in leaves ofNicotiana benthamiana.Folstrains carrying the Avr2 variants are equally virulent, showing that virulence and avirulence functions can be uncoupled. Although Avr2 is secreted into the xylem sap whenFolcolonizes tomato, the Avr2 protein can be recognized intracellularly by I-2, implying uptake by host cells.