Evidence for oral shedding of herpes simplex virus Type I (HSV) indicating endogenous viral reactivation as a measure of depressed host defense was sought in 44 critically ill surgical patients. Eighteen (41%) of these showed persistent HSV shedding. None of 50 controls showed HSV shedding, but 4 (10%) of 42 patients undergoing elective surgery showed transient postoperative viral reactivation. In the critically ill surgical patients, oral HSV shedding was not related to outcome. However, failure to develop a rise in specific HSV antibody, in the presence of viral shedding, was associated with a high mortality. This is further evidence for impairment of both cell-mediated and humoral immunity in critically ill surgical patients.