Herpes simplex virus pneumonia in immunocompromised host is difficult to diagnose with non-invasive method, and has high mortality rate. Because early diagnosis and early treatment can significantly decrease the mortality rate, the enthusiastic efforts for the early diagnosis should be done. A 41-year-old woman who took prednisolone due to mixed connective tissue disease developed gradually increasing dyspnea with radiological features of interstitial lung disease. Initially, we treated her with empirical antibiotics, but failed to improve her dyspnea. So we performed bronchoalveolar lavage and open lung biopsy. Open lung biopsy specimen showed herpes simplex virus pneumonia. Herpes simplex virus was also isolated from bronchoalveolar lavage fluid. There was both clinical and radiological improvement after treatment with acyclovir for 14 days.