The distribution and nature of sialoglycoconjugates on the surface of cells of a pancreatic carcinoma and their behavior when interacting with the sialic acid-specific lectin, limulin (LPA; from Limulus polyphemus hemolymph) were compared to those of normal pancreatic acinar cells. Fluorescence microscopy of frozen sections, using rhodaminated LPA (Rh-LPA), revealed protease-resistant binding sites evenly distributed over the cell surface of neoplastic cells, contrasting with the asymmetric distribution of sialoglycoconjugates on normal acinar cells. An asymmetric staining pattern, resembling that of normal acinar cells, was occasionally observed in tumor cells that had regained their structural polarity when in contact with the basement membranes of blood vessels. Cytochemistry, using horseradish peroxidase-conjugated (LPA (HRP-LPA), showed that the binding of limulin to neoplastic cells was less intense than that to any plasmalemmal domain of normal acinar cells. In tumor cells, local intensification of LPA binding was systematically observed on plasmalemmal regions adjacent to zymogen granules. Fixed dissociated cells, both tumor and normal, treated with Rh-LPA, retained the fluorescence distribution of Rh-LPA observed in situ. Nonfixed neoplastic cells showed lectin-induced patching of limulin binding sites and were more susceptible to agglutination by LPA than normal acinar cells.