Rationale: Hypersensitivity Pneumonitis (HP) is a lymphocytic alveolitis provoked by exposure to a variety of antigens. However, the disease occurs in only a subset of exposed individuals, suggesting that additional factors may be involved. Microchimerism has been implicated in the pathogenesis of autoimmune diseases, especially in those showing increased incidence after childbearing age. Objective: To evaluate the presence of circulating and local microchimeric cells in female patients with HP. Methods: Male microchimerism was examined in 103 patients with HP, 30 with idiopathic pulmonary fibrosis and 43 healthy women. All of them had given birth to at least one son, with no twin siblings, blood transfusions or transplants. Microchimerism was examined by dot blot hybridization (peripheral blood), and by fluorescence in situ hybridization (FISH) in bronchoalveolar lavage (BAL) cells and lungs. Results: Blood microchimerism was found in 33% of the HP patients in comparison with 10% in IPF (p=0.019) and 16% in healthy women (p=0.045). HP patients with microchimerism showed a significant reduction of DL_CO(53.5±11.9% versus 65.2±19.7%; p=0.02) compared with HP patients without microchimerism. In BAL cells, microchimerism was detected in 9 of 14 HP patients compared with 2/10 from IPF (p=0.047). Cell sorting revealed that microchimeric cells were either macrophages, CD4⁺ or CD8⁺ T-cells. Male microchimeric cells were also found in the 5 HP lungs examined by FISH. Conclusions: Our findings demonstrate that HP patients exhibit increased frequency of fetal microchimerism, confirm the multilineage capacity of microchimeric cells, and suggest that they may increase the severity of the disease.