SUMMARY After trauma, inflammatory, immunological and hormonal changes are well documented. Surgical intervention is a form of programmed trauma. Through the study of surgical patients, changes in early endogenous mediators of inflammation, immune response and tissue repair can be investigated. Here we analysed changes in serum levels of IL‐1 inhibitors, IL‐1β, IL‐6, tumour necrosis factor‐alpha (TNF‐α) and cortisol in patients undergoing elective surgery. C‐reactive protein (CRP) was measured as a marker of the acute‐phase response. Rises in serum levels of IL‐1 inhibitors. IL‐6 and cortisol were detected as early as 1 h after the intervention. Peak levels were reached between 2 and 5 h. Serum levels of IL‐6 and cortisol remained elevated for several days implying a persistent production. Serum levels of IL‐1 and TNF did not change after the intervention. CRP levels peaked on day 2. The communication system sustained by endogenous mediators is activated after surgery as shown by selective changes in IL‐1 inhibitors, IL‐6 and cortisol. These mediators have different kinetics in serum and IL‐6 is not the only early mediator detected. Some IL‐1 inhibitors might be involved in the immunological depression observed after major surgery, in the regulation of the inflammatory response or in tissue repair. IL‐6 and cortisol seem to act synergistically to activate the acute‐phase response. A systemic role for IL‐l and TNF is not evident, even if the possibility that these lymphokines may act locally is not ruled out.