Purpose: The purpose of this study was to review the course of patients with herpes simplex virus (HSV) recovered from respiratory tract secretions, and to compare the demographics, clinical characteristics, and outcomes of immunocompromised versus nonimmunocompromised patiente. Patients and Methods: Retrospective review of medical records of 42 consecutive patiente who had respiratory tract cultures positive for HSV-1 between May 1988 and August 1990 at a major university-affiliated hospital. Results: Twenty-seven patiente (64%) were not immunocompromised. On the average, the nonimmunocompromised patiente were 20 years older (mean age: 67 ± 15, p = 0.001), had a higher incidence of tobacco smoking (p = 0.04), and were more frequently endotracheally intubated prior to HSV isolation (p = 0.002). Nonimmuno-compromised patiente more frequently had bronchospasm (44% versus 7%, p = 0.01), leukocytosis (16,400 versus 6,900/mm3, p = 0.001), and difficulty weaning from mechanical ventilation (63% versus 13%, p = 0.002). Mortality was also greater in the nonimmunocompromised group (70% versus 33%, p = 0.02). In addition, for survivors, days of mechanical ventilation (8 ± 7 versus 2 ± 4, p = 0.03), length of stay in the intensive care unit (10 ± 8 versus 2 ± 4 days, p = 0.004), and length of stay in the hospital (37 ± 23 versus 16 ± 14 days, p = 0.04) were all significantly longer for the nonimmunocompromised patiente. Conclusion: These data suggest that HSV isolation from lower respiratory secretions is associated with a more severe presentation and a worse outcome in immunocompetent patiente than in immunosuppressed patiente.