A number of clinicopathological manifestations may define the presence of hypersensitivity pneumonitis. Histological study is used to establish the diagnosis and to differentiate the disease from other respiratory disorders. This case report suggests that immunohistological demonstration of the causative antigen in the lung may be a useful diagnostic approach in cases of pigeon hypersensitivity pneumonitis. A 52 year-old woman was studied. She had a prior history of pigeon exposure, and lived in an area with a high prevalence of tuberculosis. Her clinical presentation, respiratory function tests and imaging studies revealed a predominant interstitial lung disease. The results of antiavian antibodies, bronchoalveolar analysis, and other laboratory parameters were non-diagnostic. A lung biopsy showed a prominent granulomatous reaction with a sarcoid-like appearance in some areas, and an interstitial infiltration constituted by lymphocytes, plasma cells and foamy macrophages. Although the disease manifestations were compatible with hypersensitivity pneumonitis, we decided to study the causal antigen by immunohistochemistry. The use of a polyclonal antibody raised against pigeon serum showed a predominant cytoplasmic immunostaining in multinucleated giant cells and histiocytes from lung granulomas. Other respiratory disorders were reasonably excluded. Previous exposure to a known antigen may support the diagnosis of hypersensitivity pneumonitis. Although the inhalation of organic dusts may be clinically evident, the aetiology is commonly evaluated by different challenge tests or immunological methods. We propose that the study of pigeon antigen by immunohistochemistry may be used as part of the diagnostic approach for hypersensitivity pneumonitis.