To compare the diagnostic usefulness as markers of hepatocellular carcinoma (HCC) ofα1-antitrypsin, C-reactive protein, andα1acid glycoprotein (all determined by nephelometric methods), we studied 132 subjects (74 male, 58 female): 43 had mild chronic liver disease, 32 cirrhosis, 24 HCC; 33 were controls. A total of 29.2% of the patients with HCC hadα1-acid glycoprotein>100 mg/dl, 75.0% hadα1-antitrypsin<220 mg/dl, 70.8% had C-reactive protein0.0001, respectively).α1-fetoprotein performed better than all acute-phase proteins. We conclude that, due to their low specificity and/or sensitivity, none of the three acute-phase reactants tested can be recommended for diagnostic use as biological markers of HCC in Western patients.