Toward the identification of steps in the multiphasic process of human pancreas carcinogenesis we have developed a panel of monoclonal antibodies to normal and carcinogen-treated human pancreas cells. One of these, an IgG3 with strong affinity for a membrane-associated Mr 78,000 protein in fetal and adult parenchymal cells, was purified by high performance liquid chromatography, and used for the detection and characterization of tumorigenic stage in human pancreas carcinogenesis. This protein was present on the cell surface of human pancreas explants exposed to methylnitrosourea for up to 4 months and in nontumorigenic cell lines derived from these explants. It was absent in a morphologically transformed subpopulation of cells in explants treated with methylnitrosourea for longer than 4 months, in tumorigenic cell lines derived from these explants, and in primary carcinomas of human pancreas. The presence of this marker in normal pancreas adjacent to tumors, in hyperplastic cells induced by methylnitrosourea and in nontumorigenic cell lines suggests a correlation between the loss of this membrane-associated marker and cell tumorigenicity.