The expression of the gastrointestinal cancer-associated antigens CA 19-9 and CA-50 was studied in 43 ductal pancreatic carcinomas, 1 mucinous cystadenoma, 1 signet-ring-cell carcinoma, 42 pancreata with chronic pancreatitis, and 10 normal fetal and adult pancreata. The anti-CA-50 antibody gave a more intense and more uniformly distributed staining of the ductal epithelial cells than the anti-CA 19-9 antibody. Both antigens, however, exhibited the same staining pattern of ductal epithelial cells in normal pancreas and chronic pancreatitis. Well differentiated carcinomas showed a predominantly membrane-bound antigen expression, whereas moderately and poorly differentiated carcinomas gave a more diffuse cytoplasmic staining. Epithelial dysplasia could not be differentiated by the staining pattern from normal, hyperplastic, metaplastic, or neoplastic cells. The immunohistochemical reaction with these anticarbohydrate antibodies, therefore, does not allow a qualitative discrimination between chronic pancreatitis and pancreatic carcinoma. CA 19-9, which expression depends on the Lewis gene, was negative in two patients with Le(a-b-) phenotype. Although anti-CA-50 antibody was reactive with the cancer cells of these 2 patients, the staining was weak and heterogenous.