Surgical trauma is followed both by a transient increase of interleukin 6 (IL-6) concentrations in the serum and impaired function of circulating leukocytes. Perioperatively, we investigated the relationship of IL-6 concentrations in the serum with lipopolysaccharide (LPS)-stimulated cytokine production in the whole blood of patients undergoing elective major abdominal operations. In 50 patients, we found a transient increase of IL-6 concentrations in the serum. Six hours after skin incision, in vitro stimulated production of IL-6 and TNFalpha was diminished by 72% (P<0.05). A significant increase in cytokine production was observed three days postoperatively, however this was 63% below the preoperative values. Patients with high concentrations of circulating IL-6 showed a significantly lower stimulated IL-6 production than patients with low serum concentrations of IL-6. We conclude, that two opposing effects are associated with surgery: an activation leading to IL-6-release into the circulation, and a prolonged hyporesponsiveness of circulating leukocytes. These reactions are positively related.