The acute-phase reaction comprises a variety of systemic changes in response to tissue injury and infection. Synthesis of several plasma proteins in the liver undergoes dramatic changes during the acute-phase reaction. These changes are mediated by the action of cytokines, mainly interleukin 6-(IL6-) and interleukin 1-(IL1-) type cytokines. The role of these cytokines is reviewed in detail. Attention is payed to the differences recently detected between the locally and systemically induced acute-phase response--in particular, the newest findings concerning the meaning of single cytokines. Also, changes in liver metabolic enzyme expression under acute-phase conditions are discussed. The impact of cytokine and cytokine-receptor knockout or transgenic mouse models on current knowledge is provided. The role of cytokines together with that of soluble cytokine receptors in the resolution of the acute-phase response is discussed.