Transgenic tobacco plants with reduced activity of either uroporphyrinogen decarboxylase or coproporphyrinogen oxidase, two enzymes of the tetrapyrrole biosynthetic pathway, are characterized by the accumulation of photosensitizing tetrapyrrole intermediates, antioxidative responses, and necrotic leaf lesions. In this study we report on cellular responses in uroporphyrinogen decarboxylase and coproporphyrinogen oxidase antisense plants, normally associated with pathogen defense. These plants accumulate the highly fluorescent coumarin scopolin in their leaves. They also display increased pathogenesis-related protein expression and higher levels of free and conjugated salicylic acid. Upon tobacco mosaic virus inoculation, the plants with leaf lesions and high levels of PR-1 mRNA expression show reduced accumulation of virus RNA relative to wild-type controls. This result is indicative of an increased resistance to tobacco mosaic virus. We conclude that porphyrinogenesis as a result of deregulated tetrapyrrole synthesis induces a set of defense responses that resemble the hypersensitive reaction observed after pathogen attack.