Acute fibrinous and organizing pneumonia (AFOP) has recently been identified as an unusual variant of acute lung injury. We describe a man with rapidly progressive lung disease who had AFOP detected via surgical lung biopsy. The patient acutely decompensated while in the hospital and required mechanical ventilation as well as a prolonged ICU stay. He responded poorly to initial treatment and progressively worsened, but he subsequently responded very well to combined therapy with mycophenolate mofetil and methylprednisolone. The combination of corticosteroids and mycophenolate may provide a safe and effective treatment strategy for severe forms of this newly defined pulmonary syndrome.