Acute fibrinous and organizing pneumonia (AFOP) is a newly recognized form of diffuse lung injury. The histologic pattern is described as a variant of cryptogenic organizing pneumonia. AFOP is a very rare finding in a human immunodeficiency virus-infected patient. We present a unique case of a 38-year-old human immunodeficiency virus-infected patient admitted with acute respiratory distress syndrome and shock. Flexible bronchoscopy with transbronchial biopsy was consistent with AFOP. He had clinical and radiologic improvement with a course of systemic corticosteroids. This case illustrates that interstitial lung diseases, specifically AFOP, should be included in the differential diagnosis of diffuse lung diseases in patients with respiratory failure with or without shock. Flexible bronchoscopy aids in establishing the diagnosis.