Important alterations in T- and B-cell function affecting host defense and resistance to infection are found in critically ill patients and in experimental models of critical illness. In the setting of critical illness, injury, and blood loss, both T and B cells are affected, producing a relatively immunocompromised state where infection is more likely to occur, and where the ability to control the infection is lessened. Alterations in T-cell activation and cytokine production are frequently associated with hemorrhage and trauma. Injury and blood loss result in activation of CD8+ T-cell populations capable of altering bacterial antigen-specific B-cell repertoires and of suppressing the function of other T cells. The production of antibodies directed to bacterial antigens, and required for protection against extracellular bacterial infection, is diminished in models of critical illness, primarily because of disappearance of bacterial antigen-specific B-cell clonal precursors at systemic, pulmonary, and intestinal sites. Correction of the alterations in T- and B-cell function associated with critical illness would be expected to reduce the frequency of nosocomial infections in the ICU. In addition, maintenance of immunocompetence in critically ill patients will permit improved outcome should infection occur.