The cytokine interleukin-6, which has been shown to be increased in patients with burn injuries, is produced by activated monocytes and endothelial cells and has many in vitro activities, including stimulation of acute-phase protein synthesis in hepatocytes, immunoglobulin synthesis in B lymphocytes, and stimulation of growth of megakaryocytes. In 13 patients with a mean of 31% full-thickness burns, we studied the relation of serum interleukin-6 to clinical parameters and parameters of the acute-phase response and immunoglobulin production. Interleukin-6 was already elevated within hours after the injury was sustained, and it remained elevated for several weeks. All components of the acute-phase response were observed: fever, tachycardia, leukocytosis with an associated left shift, elevation of C-reactive protein and alpha 1-antitrypsin, and a decrease in albumin levels. In the second week after burn injury, immunoglobulin M levels peaked, followed by a prolonged elevation of immunoglobulin G levels. Thrombocyte counts initially decreased and rebounded to supranormal levels after 2 weeks. Interleukin-6 levels were positively correlated with acute-phase responses. We believe that the production of interleukin-6 induces the synthesis of acute-phase proteins. High interleukin-6 levels may also be an etiologic factor in the marked immunoglobulin response observed. Likewise, the relation between the megakaryocyte-promoting activity of interleukin-6 and the rebound thrombocytosis requires further investigation.