The reactivity of alpha-fetoprotein (AFP) with concanavalin A (Con A) and Lens culinaris agglutinin (LCA) was studied by crossed immuno-affinoelectrophoresis of the serum samples of 146 patients from three groups (groups I, II and III). Fifty-one patients with benign liver diseases were included in group I, 83 patients with hepatocellular carcinoma in group II, and 12 patients with carcinoma metastatic to the liver from digestive organs in group III. In group I, the percentage of Con A-reactive species of AFP was high (97 +/- 5%, mean +/- SD), but that of LCA-reactive species was very low (3 +/- 5%). The percentage of LCA-reactive species of AFP in group II (45 +/- 33%) was higher than that in group I (P less than 0.001), while the Con A binding pattern of AFP in this group, as demonstrated by immuno-affinoelectrophoresis, was similar to that of group I. The percentage of Con A-reactive species of AFP in group III (55 +/- 24%) was much lower than that in group II (97 +/- 5%) (P less than 0.001). The above results indicate that measurement of the reactivity of AFP in serum samples with Con A and LCA is useful for the differentiation of AFP species which are found in association with benign liver diseases, hepatocellular carcinoma and carcinoma metastatic to the liver.