The c-erbB-2 (neu) gene encodes a transmembrane phosphoglycoprotein (p185erbB-2) which resembles a growth factor receptor-like molecule closely related to the epidermal growth factor receptor. Overexpression of c-erbB-2 induces cell transformation in vitro. Poorer survival rates and elevated recurrence rates following treatment have been shown in patients whose breast adenocarcinomas demonstrate increased c-erbB-2 expression. Using immunoprecipitation and immunoperoxidase staining, we surveyed human cell lines for p185erbB-2. Cell lines from most tumor types (e.g. lymphomas, neuroblastomas, melanomas) demonstrated negligible p185erB-2; however, 3 of 6 pancreatic cell lines overexpressed c-erbB-2. Southern blot analysis revealed that c-erbB-2 was amplified in two of these cell lines and was both rearranged and amplified in one of them. Based on these findings, we examined tissue sections from archival specimens of primary human pancreatic adenocarcinomas. A substantial proportion of specimens had increased p185erbB-2, as judged by increased immunostaining of the tumor cells. In such pancreatic tumors p185erbB-2 may contribute to the malignant phenotype and could provide a target for immunodiagnostic or immunotherapeutic strategies.