The phenotypes of the major histocompatibility complex, loci A, B, C, and DR, were studied in 48 patients with hypersensitivity pneumonitis induced by avian antigen (pigeon breeder's lung) and the results were compared to those obtained from 200 normal subjects of similar ethnic background. Furthermore, we analyzed the delta values of the observed and expected frequencies in the deduced haplotypes of the affected population. Our results showed a significant increase of the antigen HLA-DR7 (corrected P less than 0.001) in patients with pigeon breeder's lung and an equally important difference in the delta values of the haplotypes A1-B8, A25-B14, B35-DR4, and B4-DR5. In addition, the phenotypes of locus DQ were analyzed in 21 patients and 20 controls and no apparent differences were observed. These results suggest that a multifactorial genetic susceptibility associated at least in part with the major histocompatibility complex plays in important role in the development of this disease.