During a 15-year period, 18 patients with major burns developed a wound infection due to Aspergillus. Ages averaged 28 years; extents of burn were 54% (14–97%) BSA for total surface involvement and 42% (14–85%) BSA for full-thickness injury. Pseudomonas sepsis preceded Aspergillus infection in 16 cases. Thirteen of the episodes occurred in three epidemics, each apparently related to contaminated air-conditioner ducts and filters. Treatment was based upon wound excision in all 18 patients, with recurrence initially in each. Topical and parenteral antifungal agents were never individually successful in controlling the infection. Whenever fungal sepsis involved an extremity alone and thus amputation could rid the body of the entire infected site, survival could then be achieved. The overall mortality rate was 78%. Protection of the wound from Aspergillus colonization appeared to be the only reliable method of preventing this often lethal fungus infection.