The expression of the tumor marker antigen CA 50, defined by the monoclonal antibody (MAb) C 50, was studied by the immunoperoxidase technique in formalin-fixed, paraffin-embedded tissue sections from normal pancreata, from pancreata with pancreatitis and from benign and malignant pancreatic neoplasms. The results were compared with those obtained with Mab 1116 NS 19-9. The C 50 antibody reacts, like the 1116 NS 19-9 antibody, with sialosylfucosyllactotetraose (corresponding to sialylated blood group antigen Lewisa), but also with another sugar moiety, sialosyllactotetraose. Thirty-two of 37 well- to moderately-differentiated adenocarcinomas and all cystadenocarcinomas were positive for CA 50. The staining was most intense in the apical border of the cells, and in the intraluminal mucus. The number of positive cells was smaller in poorly differentiated adenocarcinomas and only occasional cells were stained in anaplastic carcinomas. In acute and chronic pancreatitis small terminal ducts, centro-acinar cells and some large ducts stained for CA 50. In normal pancreas only a few small terminal ducts were CA-19-9-positive, whereas both ducts and centro-acinar cells were C-50-positive. Normal pancreatic tissue adjacent to carcinoma usually stained more strongly for CA 50 than the carcinoma, whereas the opposite was true for CA 19-9. Eight out of 11 CA-19-9-negative carcinomas were CA-50-positive. Serous cystadenomas and malignant islet-cell tumors were focally positive for CA 50, but negative for CA 19-9. It seems apparent that the C 50 antibody reacts with another determinant than sialylated Lewisa in CA-19-9-negative specimens, serous cystadenomas and malignant islet-cell tumors. Serum CA 50 and CA 19-9 levels were determined in 29 patients with pancreatic cancer. The sensitivity was similar for both markers (76%), and there was a positive correlation between the serum levels. However, there was no correlation between the serum levels and the histological expression of the CA 50 and CA 19-9 antigens.