The expression of blood-group-related antigens (BGRAs) in experimental primary pancreatic cancer induced by N-nitrosobis(2-oxopropyl)amine (BOP) treatment of Syrian hamsters and homologous subcutaneous transplants of this primary cancer in the cell line, PC-1, established from the primary cancer and intrapancreatic transplanted PC-1 cells were studied by histochemical and biochemical methods. Human primary pancreatic cancer; the human pancreatic cancer cell line, HPAF; and its subclones, CD11 and CD18, also were studied on a comparative basis. Histochemical analysis of BGRAs demonstrated that A, B, H, Leb, Lex, Ley, and T antigen were expressed both in vivo and in vitro in hamster and human materials in similar patterns. However, Lea, CA 19-9 and sialylated Tn antigens were not found in hamster-derived tissues. SDS-PAGE and Western blotting procedures using anti-A antigen revealed similar major bands in the membrane fractions of both human and hamster pancreatic cells between 97 and 200 kdalton. Among other human pancreatic cancer-associated antigens, TAG-72, CA 125, and 17-1A were detected immuno-histochemically in the hamster tumors both in vivo and in vitro, in a pattern similar to that seen in human pancreatic cancer. Tumor antigen DU-PAN-2, associated with human pancreatic cancer, was found infrequently in hamster pancreatic cancer specimens. These results indicate that the experimental hamster pancreatic cancer model provides a unique tool for investigating antigenicity of pancreatic cancer, particularly in relation to diagnosis and therapy.