Technical Abstract: Infection of Nicotiana obtusifolia PI#555573 by the downy mildew pathogen Peronsopora tabacina resulted in a compatible interaction, in which P. tabacina invaded and freely colonized host leaf tissue. This interaction became incompatible 5-6 days later, with the appearance of necrotic lesions (NLs) and inhibition of pathogen growth and subsequent sporulation. NL development depended upon the presence of P. tabacina in host tissue, was not due to the effects of other microbes, and occurred co-incident in time with the pathogen's ability to produce asexual sporangia on a susceptible N. obtusifolia. Inhibition of the necrotic response by CoCl2 (a calcium channel blocker), and pathogen-induced transcription of a defense related gene (PR-1a), suggested that necrosis was due to hypersensitive cell death in the host. N. obtusifolia accession PI#555543 did not exhibit hypersensitivity upon infection by P. tabacina, and instead developed characteristic symptoms of tobacco blue mold disease ' chlorotic lesions accompanied by abundant pathogen sporulation. Pathogen reactions scored on PI#555573 X PI#555543 F2 progeny inoculated with P. tabacina sporangia indicated that the resistance phenotype was due to a single gene from N. obtusifolia 555573, which we have named Rpt1. To date, Rpt1 is the only gene known to confer a hypersensitive response (HR) to P. tabacina infection in any species of Nicotiana. A survey of wild N. obtusifolia revealed that the HR to P. tabacina was expressed in the progeny of 7 out of 21 (33.3%) plants collected in southern Arizona, but was not observed in the progeny of plants originating from Death Valley National Park in California and the Big Bend National Park in Texas.