A lectin was isolated from the external mucus of fish, Genypterus blacodes. This is the first lectin isolated from fish. The molecular weight of the lectin, determined by gel filtration, was approximately 32 000, whereas 8 000 was indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of 2-mercaptoethanol. Amino acid analysis demonstrated that the lectin contained large amounts (near 30% of the residues) of lysine, but no tryptophan. The lectin agglutinated mouse, rabbit and human erythrocytes at a concentration of 15.6 micrograms/ml. An inhibition test revealed that the lectin was strongly inhibited by N-acetyl-glucosamine, mucin and orosomucoid. Binding studies performed with iodinated asialo-orosomucoid indicated that the lectin contained a high affinity binding site with a dissociation constant of 1.1 X 10(-8) M. The lectin required the presence of calcium ion for both its hemagglutination and binding activity.