Severe trauma or thermal injury induce the appearance of serum factors that suppress cell-mediated immunity, as measured by lymphocyte proliferative response. This phenomenon has been shown to correlate with a higher incidence of infectious complications after accidental and operative trauma. We have found recently that moderately severe hemorrhage alone in "untraumatized" and unanesthetized rats was sufficient to bring about the appearance in the blood of such an immunosuppressive factor. It is the objective of the proposed research to (1) define the conditions necessary for suppressive factor production by examining serum suppressive activity after hemorrhage of graded severity; (2) isolate a sufficient amount of this suppressive factor, purify it to electrophoretic homogenity, and determine its molecular weight; (3) ascertain the mechanism(s) which underlie the immunosuppressive action of the serum factor(s) by determining its effect on the generation and proliferation of helper and suppressor T cells, on interleukin-2 production by stimulated lymphocytes as well as determining possible counter actions by exogeneous interleukin-2. The results generated from the proposed experiments should provide information which may permit the development of methods to better identify and correct the suppression of lymphocyte proliferative capacity which exists after trauma and hemorrhage, leading to decreased rates of infection, morbidity and mortality after trauma.