Monoclonal antibodies (MAbs) were selected for specific binding to spent media of cultured tumor cells. Out of more than 12,000 hybridomas screened, 19 were selected in preliminary inhibition assays for secretion of MAbs which detected antigens in cancer patients' sera. Antibody CO 29.11, which was studied in detail, bound to an antigen shed and expressed by adenocarcinoma cells of colon, stomach, pancreas and urinary bladder. CO 29.11 bound to purified sialylated Lewis a (Lea) antigen but to a different epitope and with a higher binding affinity than the MAb CA 19-9. CO 29.11 but not CA 19-9 bound weakly to unsialylated Lea antigen. In double-determinant radioimmunoassay with sera of patients with colorectal carcinoma, CO 29.11 was found to be a more sensitive marker than CA 19-9 for the detection in serum of sialylated Lea antigen.