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This study determined the effect of femoral nailing on the expression of monocyte Class II antigens and interleukin-10 release and sought to differentiate any differences in the release of these elements of immune reactivity in patients undergoing reamed and unreamed nailing. Thirty-two patients presenting with an acute femoral fracture were studied. In 15 patients, the femoral fracture was stabilized with a reamed technique and in 17 patients with an unreamed technique. Venous blood samples were taken at presentation, at anesthetic induction, immediately after nail insertion, and subsequently at 1, 4, and 24 hours and at 3, 5, and 7 days after surgery. Serum interleukin-10 was measured by an enzyme-linked immunosorbent assay, and monocyte human leukocyte antigen-DR expression was quantified by flow cytometry. Serum interleukin-10 release and human leukocyte antigen-DR expression on monocytes showed a clear response to the nailing procedure. The group of patients undergoing a reamed femoral nailing procedure showed significantly higher interleukin-10 release and a significant depression in the expression of human leukocyte antigen-DR on monocytes compared with those whose nail had been inserted unreamed. One patient in the reamed femoral nailing group died of adult respiratory distress syndrome 3 days after injury. Reamed intramedullary nailing appears to be associated with greater impairment of immune reactivity than is the unreamed nailing technique.