Objective: Primary events such as severe injury and elective surgery cause a deterioration of the immune response measurable by reduction of expression of HLA-DR on monocytes or ex vivo LPS-induced TNFalpha production. The further influence of secondary surgery after severe injury on the immune response remains unresolved. Design: Prospective observation study. Setting: Surgical intensive care unit of an university hospital. Patients: Sixteen severely injured patients with an ISS >25 points. Measurements and results: On day 1 after trauma and immediately before secondary surgery, mean fluorescence intensity (MFI) of HLA-DR expression on monocytes and TNFalpha ex vivo synthesis was significantly reduced compared to healthy donors. Overall, surgical intervention during the second week after trauma caused no further reduction of HLA-DR expression on monocytes and of the ex vivo TNFalpha-syn-thesis. However, major surgery such as intramedullary nailing or pelvic osteosynthesis caused reduction of the HLA-DR expression and TNFalpha-synthesis, whereas, minor surgical interventions such as osteosynthesis on peripheral joints exhibited no significant effects on the immune response. Surgical intervention performed to clear septic foci normalised immune response by elevating HLA-DR expression on monocytes and ex vivo TNFalpha synthesis. Severe injury caused elevated serum IL-10 levels, whereas secondary surgery did not induce a further increase in serum IL-10 levels. Conclusion: This study shows that initial trauma as well as major secondary surgery causes a suppression of immune functions, whereas minor secondary surgery does not cause significant immune disturbance.