The marine sponge Anthosigmella varians contains proteins that agglutinate human erythrocytes irrespective of their ABO group antigens. The hemagglutination reaction depends on divalent cations and is not inhibited by L-arabinose, D-xylose, L-rhamnose, D-galactose, D-glucose, L and D-fucose, N-acetyl-D-galac-tosamine, N-acetyl-D-glucosamine, methyl-alpha-D-mannopiranoside, D-cellobiose, lactose, maltose, melibiose nor raffinose (33 mM each). A partial purification of the hemagglutinins with 31-fold increase in SA and 80% recovery of activity was obtained after gel filtration and ion-exchange gradient elution chromatography. Hemadsorption experiments carried out with the semipurified fraction using glutaraldehyde-fixed human erythrocytes suggest that proteins with molecular weight of 90 and 34 kDa participate in this reaction.