To compare the diagnostic usefulness as markers of hepatocellular carcinoma (HCC) of alpha1-antitrypsin, C-reactive protein, and alpha1-acid 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 had alpha1-acid glycoprotein > 100 mg/dl, 75.0% had alpha1-antitrypsin > 220 mg/dl, 70.8% had C-reactive protein > 5 mg/L. In cirrhotics, frequencies were 3.1, 50.0 and 59.4%, respectively; in patients with mild chronic liver disease, 14.0, 11.6, and 32.6% (chi2 12.3, p < 0.01; chi2 47.3, p < 0.0001; chi2 38.0, p < 0.0001, respectively). alpha1-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.