Histamine release was performed on 28 patients with allergic bronchopulmonary aspergillosis (ABPA) in various stages and on 14 patients with mold-sensitive asthma, by using Aspergillus antigens, other mold antigens, and anti-IgE. Total serum IgE, IgE and IgG antibodies to Aspergillus fumigatus (Af), and end point cutaneous titration for Af were determined for each patient. There was greater histamine release to Aspergillus mix (p = 0.0000) and anti-IgE (p = 0.047) in patients with ABPA than in patients with mold-sensitive asthma. Patients with stages IV and V ABPA had greater histamine release to Aspergillus mix than patients with stage I, II, or III ABPA (p = 0.0014). There was greater histamine release to other molds in ABPA patients than in mold-sensitive asthmatics. There was no correlation between histamine release to Aspergillus mix and total serum IgE, IgE or IgG antibodies to Af, ratio of IgE and IgG antibodies to Af to total IgE, or cutaneous end point titration for Af in ABPA patients or mold-sensitive asthmatics. Peripheral basophils from ABPA patients demonstrated marked hyperreactivity as evidenced by histamine release to Aspergillus antigens, other molds, and anti-IgE. This hyperreactivity is the first cellular difference recognized in ABPA patients when compared to mold-sensitive asthma patients. If this hyperreactivity is manifested by mediator release from other cells such as pulmonary mast cells, which would be in close contact with growing Af, a possible mechanism for pulmonary response in ABPA would be suggested.