Seventy-nine patients with cystic fibrosis (CF) were evaluated and were followed in a longitudinal, prospective fashion during a 6-year period for the development of immune parameters indicating Aspergillus fumigatus (Af) sensitization and allergic bronchopulmonary aspergillosis (ABPA). Although four patients developed frank ABPA, there was considerable variability in immune parameters in non-ABPA. Twenty-four patients became skin test positive to Af with none losing skin reactivity. Twenty-five patients developed serum precipitins to Af, whereas 12 patients lost their precipitins. Of 15 patients with an elevated total serum IgE of greater than or equal to 2 SD, five demonstrated a marked decline of at least 40%. Three of 16 patients with IgE-Af became negative, whereas eight of 27 patients lost their IgG-Af. None of these patients had received corticosteroid therapy that could have accounted for the findings. Thus, patients with CF frequently lose evidence of Af sensitivity spontaneously without corticosteroid intervention. The diagnosis of ABPA in CF should not be based solely on serology and skin test results, since at any point in time, patients with CF may demonstrate variable responses to Af.