The authors report a fatal outcome in a 4-year-old boy with herpes simplex virus (HSV) pneumonia and ependymoma. The patient had respiratory distress that worsened despite antibiotic treatment. Bronchoalveolar lavage showed intranuclear viral inclusions, and culture was positive for HSV type 1. His T-cell count was significantly decreased. Although acyclovir and foscarnet were given, the patient died. Postmortem examination showed HSV pneumonitis with severe alveolar damage and severe involutional changes of the thymus with absence of Hassall's corpuscles. HSV must be considered in the differential diagnosis of patients with interstitial pneumonia and T-cell deficiency, especially after craniospinal irradiation.