To elucidate the involvement of hepatocyte growth factor (HGF) in systemic inflammatory response syndrome (SIRS) and sepsis, we investigated the plasma levels of HGF, as well as those of various proinflammatory and anti-inflammatory cytokines, in 50 patients who visited our emergency department (ED). The patients were divided into four groups, depending on the existence of SIRS and infection: group 1 (G1), no infection and no SIRS; group 2 (G2), infection and no SIRS; group 3 (G3), no infection and SIRS; and group 4 (G4), infection and SIRS (e.g., sepsis). We found that plasma HGF levels in G4 were significantly higher than those in the groups without infection (G1 and G3). However, the correlations between HGF and other cytokines were comparatively low compared with those between any other pairs of cytokines, suggesting independent regulation of HGF production in vivo. High plasma HGF was significantly correlated with the presence of infection and with serum total bilirubin (TB) level on multivariate logistic regression analysis. Considering HGF's known functions, we speculated that high plasma HGF levels may indicate the occurrence or necessity for tissue protection and regeneration after acute systemic insults in sepsis.