Murine monoclonal antibodies were generated against FG, a human pancreatic carcinoma (HPC) cell line. Of the six monoclonal antibodies, five (S3-15, S3-23, S3-41, S3-60, and S3-110) reacted by indirect immunoperoxidase assays with HPC of the ductal type, and another (S3-53) reacted with both ductal and acinar HPC. Strong reactivity was also found with tumors of the stomach, colon, mouth, lung, and cervix, while a large panel of normal human tissues displayed little reactivity. Indirect immunofluorescence staining revealed that, except for S3-23, the antigens recognized by these antibodies are expressed at the cell surface. Immunoprecipitation of metabolically radiolabeled FG cells indicated that the epitopes recognized by these antibodies are carried by distinct proteins or glycoproteins, differentiated on the basis of the apparent molecular weight and/or subunit composition as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This panel of antibodies will be useful to study antigenic variations associated with malignant cell transformation in HPC as well as other tumors.