BACKGROUND : Hypersensitivity pneumonitis is a complex syndrome characterized by non-Immunoglobulin E-mediated inflammation of lung parenchyma in response to an antigen. METHODS : A 60-year-old white man presented with acute onset of hypoxia, dyspnea, and nonproductive cough. After extensive workup, he was diagnosed with hypersensitivity pneumonitis. We present the case of a patient with refractory hypersensitivity pneumonitis not responsive to standard immunosuppressive therapy, who was successfully treated with rituximab. CONCLUSIONS : Hypersensitivity pneumonitis is a multifaceted syndrome characterized by an exaggerated immune-mediated response to an antigen. Currently, the most common treatment for an acute exacerbation of the syndrome is withdrawal of the offending antigen and systemic corticosteroids. However, despite their widespread use, the efficacy of steroids in treating acute hypersensitivity pneumonitis is poor. CONCLUSIONS : Rituximab could be considered as a salvage therapy in cases of severe hypersensitivity pneumonitis unresponsive to standard therapy, especially in patients with high risk of death.