Lily leaf spot, a fungal foliar disease caused by Pseudocercosporella inconspicua, leads to premature senescence of aboveground tissues in Lilium grayi. At Roan Mountain, North Carolina/Tennessee, the disease was most prevalent and most severe in seedlings and juveniles. In the two growing seasons assessed, 59 and 70% of mature plants experienced disease-induced premature senescence. Plants with disease lesions on seed capsules matured fewer capsules and had fewer seeds per capsule, and seeds had reduced viability. Disease prevalence over the growing season followed a sigmoidal pattern typical of polycyclic epidemics. Plants with low and high disease severity occurred in clusters whose locations were stable across growing seasons. Prior to the recent description of lily leaf spot, L. grayi was already considered threatened or endangered in each of the three states where it naturally occurs. Therefore, this infectious disease poses conservation and management difficulties because increases in plant density can be expected to lead to enhanced disease transmission. Lily leaf spot of L. grayi is best characterized as an annually recurring epidemic because of high prevalence rates, strong impacts on all life stages, and reductions in seed production and viability.