We report a cluster of 3 cases of nosocomial herpes simplex virus type 1 (HSV-1) pneumonia occurring in close temporal and physical proximity during a 1-week period, which suggested a common source. HSV-1 nosocomial pneumonia occurs in immunocompetent intubated patients and presents as otherwise unexplained profound and/or prolonged hypoxemia (decreased F(IO2), increased P(O2), and decreased A-a gradient) and "failure to wean." The diagnosis of HSV-1 pneumonia is determined by demonstration of characteristic cytopathologic findings (Cowdry type A inclusion bodies) in distal respiratory epithelial cells from bronchoscopic specimens. Acyclovir therapy results in rapid improvement and ability to wean.