Two lectins with affinity for hog A + H blood group substance were extracted from the Mediterranean sponge Geodia cydonium. One, termed Geodia lectin I, was purified to near homogeneity by lactose elution from a column of hog A + H coupled to Sepharose 4B. Geodia lectin I was a glycoprotein (carbohydrate content about 14%) with m.w. of about 60,000 and an isoelectric point of pH 4.4. Subunits of about 15,000 daltons were linked by disulfide bonds. The lectin precipitated with various snail galactans composed entirely of DGal and LGal, to a slight degree with guaran, which has DGal alpha 1 leads to 6 in a terminal nonreducing position, and with blood group substances. Of 42 sugars tested, only lactose, dGal beta 1 leads to 4 DGlcNAc, DGal beta 1 leads to 3DGlcNAc, DGalNAc, inhibited precipitation. In view of the relatively high concentration of those disaccharides that inhibited relative to other lectins, the specificity of interaction is thought to be via beta-linked DGal residues that are part of a more complex combining site. Geodia lectin I was mitogenic for human peripheral blood lymphocytes with an optimal concentration of about 5.6 micrograms/ml if serum was omitted for the first 24 hr of culture to allow "triggering." Fetal calf serum apparently contained a high concentration of substances that inhibited mitogenicity and hemagglutination by Geodia lectin I, presumably by specifically interacting with the binding site.