We studied the usefulness of Lens culinaris agglutinin A-reactive α-fetoprotein (AFP)-L3 and erythroagglutinating phytohemagglutinin-reactive AFP-P4 as a tool for early detection of hepatocellular carcinoma (HCC) in a mass screening programme. Eight hundred and eight subjects from a total of 24 839 subjects, who attended the mass screening for elderly were considered a high-risk group for HCC on the basis of abnormal aspartate aminotransferase (AST) serum levels and/or zinc sulphate turbidity test (ZTT). They were tested for serum AFP level, 33 examinees with serum AFP levels above 20 ng ml - 1 were further screened by AFP-L3 and AFP-P4 analysis. Seven people were found to have AFP L-3 and/or AFP P-4 above the cutoff values of 15 and 12%, respectively, and further evaluated as a population at extremely high-risk of having HCC. Five people were diagnosed with HCC and two people were followed up, the detection rate being 0.02%, which is comparable to that of ultrasound-based mass screening of HCC. Ultrasound scanning of the liver at the time of initial screening with liver function tests failed to detect space-occupying lesions of the liver. The cost of detecting one case of HCC was calculated at US $28 790, which is one-fourth of the cost of ordinary mass screening for HCC. Thus, the inclusion of the assay for AFP-L3 and AFP-P4 as well as AST, ZTT and AFP in mass screening for HCC was found highly cost effective.