Traumatic tissue injury of infection provokes a systemic inflammatory response, termed the acute-phase response, which is accompanied by hepatic synthesis of certain plasma proteins. Increased levels of serum amyloid A (SAA), C-reactive protein (CRP), and fibrinogen have been observed during the acute-phase response. One possible mediator of the acute-phase response is interleukin-1, a pro-inflammatory monokine released in response to traumatic tissue injury or infection. There is evidence that partially purified macrophage supernatants containing interleukin-1 activity stimulate hepatocyte secretion of SAA, CRP, and fibrinogen. The effect of interleukin-1 on mouse liver serum amyloid A mRNA levels was investigated. The acute-phase response was induced in mice by intraperitoneal injection of interleukin-1 obtained from cloned murine recombinant DNA. We monitored SAA mRNA levels using DNA/RNA dot blot hybridization. Interleukin-1 stimulated a dose-dependent increase in SAA mRNA levels compared to unstimulated controls. In contrast, mRNA levels for apolipoprotein E (a constitutive hepatic protein not produced as part of the acute-phase response) were unchanged under identical conditions. Interleukin-1 also induced SAA mRNA in an endotoxin-resistant strain of mice (C3H/HeJ), indicating that this stimulation was not due to endotoxin contamination since endotoxin alone was unable to induce SAA mRNA in these mice. These results indicate that recombinant interleukin-1, when injected intraperitoneally into mice, induced specific production of SAA mRNA and hence one phase of the acute-phase response.