The respiratory flora of patients with cystic fibrosis (CF) frequently includes Aspergillus, and 30% of their serum samples have been observed to contain precipitating antibody to this fungus. Serum from 61 CF patients, 60 healthy persons, and three patients with CF and allergic bronchopulmonary aspergillosis was studied, using a quantitative assay for antibody to A fumigatus. Although CF patients had significantly higher levels of Aspergillus antibody, some antibody was found in all serum samples from normal individuals. Binding was immunologically specific for A fumigatus. Serum IgE levels and dermal reactivity to Aspergillus were similar in both CF and normal subjects. Increased levels of Aspergillus antibody in CF patients probably reflect pulmonary colonization, which only rarely causes infection or sensitization.