The pathogenesis of hyperasialoglycoproteinemia in cirrhosis and liver cell carcinoma was investigated by measuring the amount of asialoglycoprotein receptor in hepatic tissues from 30 patients with either cirrhosis or a malignancy. The asialoglycoprotein receptor activity in the cirrhotic liver was 770 +/- 423 U/g liver, i.e., 28% of the control value (2770 +/- 731 U/g liver). Receptor activity was negligible in tissues from patients with either liver cell carcinoma or metastatic tumor. The receptor levels in noncirrhotic and cirrhotic tissues in close proximity to liver cell carcinoma were 2281 +/- 659 and 1134 +/- 473 U/g liver, respectively. There was a close correlation between serum asialoglycoprotein levels and the size of the tumor mass in patients with liver cell carcinoma. Our results suggest that decreases in the asialoglycoprotein receptor levels may lead to an accumulation of serum asialoglycoproteins in patients with cirrhosis or liver cell carcinoma, or both.