Objective: To investigate cellular and humoral immunity in children immediately after severe head injury and during the early recovery period. Design: Prospective, observational study with factorial design, Setting: Pediatric ICU of a university teaching hospital, Patients: Fifteen children (median age 9.6 yrs, range 1.7 to 18) with head injury and Glasgow Coma Score of less than or equal to 7. Interventions: None. Measurements and Main Results: Skin testing with seven standard antigens was performed and blood samples were obtained for the following measurements: total lymphocyte count and subsets; proliferative response to phytohemagglutinin, concanavalin A, and pokeweed mitogen; and immunoglobulin concentrations on days 1, 7, and 14 and 3 months after injury. The effect of patient plasma on phytohemagglutinin-induced proliferative responses of normal donor lymphocytes was also assessed at these times, Anergy was present in 71% of patients on day 1, 54% of patients on day 7, 31% of patients on day 14, and 18% of patients at 3 months. Total, helper, and suppressor T-cell counts were decreased on day 1, and the T-cell response to phytohemagglutinin was decreased on days 1, 7, and 14 compared with values at 3 months. B-cell counts were increased on day 1, followed by an increase in serum immunoglobulin concentrations 1 to 2 wks later. The B-cell response to pokeweed mitogen was unchanged over the 3-month study period. The phytohemagglutinin responses of normal donor lymphocytes were decreased when incubated with patient plasma obtained on day 7 after injury. Conclusions: Severe head injury in children is associated with depressed cell-mediated immunity. Plasma immunosuppressive factors may contribute to T-cell dysfunction.