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 quantities into the tissue culture milieu. In this group, 4 glycolipid antigens of colon carcinoma, including a monosialoganglioside, and 5 glycoproteins of melanoma were detected in tissue culture supernatants. Antigens of the 2nd group could not be detected in tissue culture supernatants. This group included 1 colorectal carcinoma antigen, the nature of which is unknown, and a glycoprotein of melanoma cells.