Basophil histamine release by P. aeruginosa standard antigen was examined in cystic fibrosis patients chronically infected with mucoid P. aeruginosa (CF +P) and with pronounced antibody response against these bacteria, and in patients without P. aeruginosa infection (CF +P). All the patients showed eosinophil counts and total IgE, which did not differ significantly from that of normal persons. In the absence of patient's sera, histamine release was only found in two patients in the CF +P group, indicating that type I allergy to P. aeruginosa is not predominating in cystic fibrosis. In the presence of patients' sere significantly more of the CF+P patients responded to P. aeruginosa with histamine release compared with the CF-P patients. The response was lost by complement inactivation and regained by reconstitution of the complement activity. The involvement of a type III-mediated complement-dependent histamine release is therefore suggested in the pathogenesis of lung damage in cystic fibrosis.