We aimed to investigate the role of IL-6 as a mediator of the acute phase response (APR) in man; to assess the effect of under-nutrition on serum/plasma IL-6 levels; and to assess the value of IL-6 as a prognostic indicator by measuring IL-6 in timed venous samples taken from surgical patients and from protein deficient and control rats post-turpentine injections. Serum IL-6 rose in all surgical patients within 2-4h of incision. Peak levels differed among the groups and correlated significanlly with duration of surgery (r = 0.75, p<0.001). CRP did not rise in some patients and discriminated poorly among the groups. Patients who developed complications had higher IL-6 values at 24h post-incision than those making uneventful recoveries. Protein depleted rats had a significantly slower IL-6 response than controls. Serum IL-6 is a sensitive, early marker of tissue damage which might help to predict the development of surgical complications. Under-nutrition affects the IL-6 response in rats and may do so in man.