This study demonstrates that immunodepressed trauma patients' monocytes produce elevated interleukin-6 to adherence, bacterial, and cytokine stimulation compared to immunocompetent trauma patients' or normals' monocytes, suggesting their in vivo preactivation possibly mediated by the hyperimmunoglobulinemia which characterizes these patients. Furthermore, stimulation of monocytes through cross-linking their Fc gamma RI induces and augments interleukin-6 (IL-6) production to subsequent stimulation both in trauma patients' (P less than 0.001) and in normals' (P less than 0.001) monocytes. As we reported earlier, immunodepressed trauma patients have an increased proportion of Fc gamma RI-bearing monocytes in their total monocyte population and here we show that those Fc gamma RI+ monocytes produce significantly elevated interleukin-6, suggesting a relationship between elevated monocyte interleukin-6 production and Fc gamma RI triggering. Interleukin-6 induction by FcRI stimulation is not mediated solely by FcRI-induced M phi tumor necrosis factor alpha, IL-1 alpha, or IL-1 beta production and is independent of M phi prostaglandin E2 levels. Therefore, FcRI stimulation-induced elevated M phi IL-6 might contribute to the increased immunoglobulin levels posttrauma.