Herpesvirus infections are commonly seen in immunosuppressed patients and may account for considerable morbidity and some mortality. We prospectively studied 52 patients with severe burn injuries in order to determine the prevalence of viral infections in this group of patients. Serologic testing was done each week to diagnose primary and reactivation infections. Twenty-seven of 52 patients (52%) became infected with either herpes simplex virus (HSV) or cytomegalovirus (CMV) or both. HSV infection was associated with older age, tracheal intubation, facial burn, inhalation injury, length of hospitalization, and the presence of full-thickness burn. CMV infection was associated with duration of hospitalization and full-thickness burn. Transfusion of blood products was not correlated with an increased incidence of primary or reactivation CMV infections. There was a significant correlation between the presence of these viral infections and bacterial sepsis (p less than 0.05). There was no significant association of HSV or CMV infections with mortality.