Alpha-fetoprotein reactive to Pisum sativum agglutinin levels (AFP-R-PSA) was measured in sera from 124 patients with hepatocellular carcinoma (HCC) and 54 patients with benign liver diseases (BLD). The level of AFP-R-PSA in the HCC group (42% +/- 22%) was significantly higher than that in the BLD group (10% +/- 8%). When an AFP-R-PSA level above 25% was used as a value highly suggestive of HCC, the sensitivity of the test was 82%, the specificity was 96%, the accuracy was 86%, and the positive prediction value was 98%. The positive rates of AFP-R-PSA in HCC patients with a serum AFP level below 100 micrograms/L and with a serum AFP level below 400 micrograms/L were 78% and 84%, respectively. Corresponding value was 74% for 31 patients with a tumor size less than 5cm. If AFP was combined with AFP-R-PSA, the detection rate of small HCC in this study would be increased from 32% to 87%. These data indicate that measurement of AFP-R-PSA is useful for the differentiation of BLD and for the early diagnosis of HCC.