The possible role of Interleukin 6 (IL-6) and tumour necrosis factor (TNF) in the regulation of the acute phase response to injury was studied in thirteen subjects undergoing elective surgery or suffering from multiple accidental injuries. The temporal changes in the circulating concentrations of these cytokines were related to the circulating acute phase protein concentrations (C-reactive protein and alpha 1 antichymotrypsin), white cell count, blood loss and duration of surgery. Circulating acute phase protein concentrations rose in all subjects during a thirty hour period following injury but none of the subjects showed a detectable rise in circulating concentrations of TNF. Peak circulating concentrations of IL-6 were detected between 4-6 hours after surgery/trauma but these showed a poor correlation with blood loss, fever, white cell count or duration of surgery. The peak concentrations of IL-6 typically occurred before the rise in circulating acute phase protein concentration. The data do not suggest a role for circulating TNF in the regulation of the acute phase response to injury. In contrast, IL-6 appears to be variably involved in the acute phase response but its precise role in mediating fever, leucocytosis and synthesis of acute phase proteins is as yet uncertain.