The rate of clearance of inhaled 99mTc-DTPA was measured in 20 nonsmoking pigeon fanciers and 7 control subjects. The degree of their avian contact and pigeon-related symptoms were noted, humoral immune response in the form of IgG antibody to pigeon gamma globulin was quantified, and diffusing capacity and total lung capacity were measured. Thirteen fanciers who had a high level of antibody had increased rates of clearance of 99mTc-DTPA (mean half-time clearance of 16.8 [+/- SEM 2.02] min [p = 0.001]) even if they were asymptomatic and even if their diffusing capacity and total lung capacity were normal. Seven control subjects without exposure to pigeon-derived antigens had normal clearance (mean 72.6 [+/- 5.98] min), and seven fanciers with antigen exposure but without an antibody response had intermediate rates of clearance (mean 42.57 [+/- 5.11] min). Clearance was not directly related to the indices of intensity and duration of antigen exposure. The measurement of rate of clearance of 99mTc-DTPA in pigeon fanciers can identify an alteration in pulmonary integrity more subtle than found with conventional pulmonary function tests and may therefore be a useful test for studying the pulmonary response to inhaled antigen and for detecting the earliest stages in the evolution of hypersensitivity pneumonitis.