Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS) and other exogenous and endogenous molecules, and is thought to contribute to defense mechanisms against infections. Our objective was to elucidate the clinical significance of TLR4 in acute infectious diseases by analyzing its sequential expression on CD14+ monocytes. Peripheral blood samples were obtained from 36 patients with acute infectious diseases on admission and after treatment within certain intervals. The TLR4 expression on CD14+ monocytes was analyzed using flow cytometry and was presented as a mean fluorescence intensity (MFI). TLR4 expression during the acute phase of infection was highly enhanced compared to that of normal subjects (MFI: 22.1 vs 8.5). TLR4 expression was promptly reduced to normal levels in parallel with the disease improvement. In patients who died despite treatment, the enhancement of TLR4 expression during the acute phase was less prominent compared to those who survived (MFI: 14.6 vs 23.5) and its sequential change was also subtle. These results indicate that monocytes respond to acute infections by the induction of TLR4 expression and that a poor response may be associated with a poor prognosis.