The AVR9 peptide of the fungal pathogen Cladosporium fulvum and the INF1 protein of the oomycete pathogen Phytophthora infestans elicit the hypersensitive response (HR) on Cf9 tomato or Cf-9 transgenic tobacco and on all cultivars of tobacco, respectively. Expression of either the functional Avr9 or inf1 genes from engineered potato virus X (PVX) genomes resulted in localized HR lesions on tobacco plants responsive to the elicitors and inhibited spread of the recombinant virus. In contrast, PVX derivatives producing mutant forms of AVR9 and INF1 with reduced elicitor activity caused systemic necrotic and/or mosaic symptoms, and were unable to inhibit PVX spread. These results demonstrate that HR is a highly versatile defense mechanism active against unrelated pathogens irrespective of the HR-inducing agent, and that resistance to recombinant PVX in tobacco is correlated with the strength of the transgene-encoded elicitor.