Serum alpha-fetoprotein levels were determined in patients (268) with liver disease. Markedly elevated concentrations (greater than 100 micrograms/l) were found in twelve patients with malignant tumours and two with cirrhosis. Molecular variants of alpha-fetoprotein were distinguished by lectin affinity chromatography of these sera. Reversible binding to concanavalin A (86 +/- 5%) and to lentil agglutinin (61 +/- 19%) conformed to expected values for primary hepatocellular carcinoma except in one patient with a metastatic carcinoma whose alpha-fetoprotein binding to concanavalin A was similar to non-liver alpha-fetoprotein (44 +/- 13%), and the two patients with cirrhosis in whom binding to lentil agglutinin was typical for benign liver disorders (less than 20%). Since low levels of serum alpha-fetoprotein and non-characteristic alpha-fetoprotein binding patterns assisted in the regrouping of eleven out of 24 patients initially thought to have primary hepatocellular carcinoma, it was concluded that alpha-fetoprotein determination and lectin affinity chromatography are helpful in distinguishing primary hepatocellular carcinoma from metastatic and benign liver diseases. Slight increases in the alpha-fetoprotein level in the presence of serum hepatitis B surface antigen indicated seven patients at risk for primary hepatocellular carcinoma who should be monitored frequently.