Methacholine inhalation challenges were performed in five groups: 14 patients with history of farmers' lung disease (FLD), nine well farmers with precipitating antibodies to Micropolyspora faeni antigen, 11 normal subjects, 12 asthmatic patients, and 10 patients with interstitial lung disease (ILD) other than hypersensitivity pneumonitis. After calculating the mean areas under the dose-response curves, FLD patients had a significantly greater degree of methacholine sensitivity than did well farmers with M. faeni antibody and normals. However, the methacholine sensitivity of FLD patients was indistinguishable from a group of patients with ILD and significantly less than the asthmatic group. Fifty percent of patients with FLD had positive methacholine challenges (≥20% decrease in their 1-sec forced vital capacity [FEV 1 ] from the control FEV 1 ). Hyperirritable airways was a common finding in FLD.