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The data generated in a rat burn model supports the following conclusions: (1) There is a period of normal immune responsiveness surrounding day 6, in spite of peaks of immunosuppression before and after that time. (2) The spleen in burned animals is hypertrophic. This is due to its role as a filter (necrotic particles seen in macrophagesl and as a “germ reservoir” (spleen culture studies). Impairment of immune function in spleen cells is important since before day 6 there is an inhibition of antibody production with no alteration in lymphocyte transformation; after day 6, lymphocyte transformation and antibody production are both impaired. (3) Most important to the clinical treatment of burns, all of these phenomena are diminished or abolished by early removal of the burned tissue. The profile of immune depression in burned rats therefore seems to show two stages: before and after day 6. During the first, stress and prostaglandins from burned skin are probably the cause of immune depression; during the second, burn toxins and prostaglandins from the spleen cells are probably the cause.