Nitric oxide (NO) from artificial NO donors induces cell death through complete inhibition of mitochondrial respiration of hepatocytes. Treatment of hepatocytes with lipopolysaccharide (LPS) and cytokine mixture (interferon gamma and tumor necrosis factor alpha) not only results in NO production but also causes cellular respiration suppression and cell death in hepatocytes. NG-monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase, inhibits hepatocyte NO synthesis but cannot prevent hepatocytes from LPS and cytokine mixture-induced cellular injuries. Similarly, some metabolic intermediates capable of inhibiting hepatocyte NO synthesis cannot block LPS and cytokine mixture-mediated cellular injuries in hepatocytes. These results imply that lipopolysaccharide and cytokine mixture-induced cellular injuries and NO syntheses are parallel events, NO is not involved in LPS and cytokine mixture-induced cell damage.