Many but not all of the cell surface antigens studied were released into tissue culture medium of human colorectal carcinoma and melanoma cells maintained in vitro. Two groups of monoclonal antibody-defined antigens are described. One group is composed of molecules that are released easily and in large quantitites into the tissue culture milieu. In this group, four glycolipid antigens of colon carcinoma, including a monosialoganglioside, and five glycoproteins of melanoma were detected in tissue culture supernatants. Antigens of the second group could not be detected in tissue culture supernatants. This group included one colorectal carcinoma antigen, the nature of which is unknown, and a glycoprotein of melanoma cells.