In the present study we sought to determine by Northern blot analysis and mRNA in situ hybridization whether gene expression of heat shock proteins (HSPs) (HSP 89αa, HSP 89β, HSP 70, and ubiquitin) is altered in pancreatic carcinoma, compared to control tissues (normal pancreas and chronic pancreatitis tissue). HSP 89α was selectively overexpressed in pancreatic carcinoma, and tumor cells were shown to contain the largest amount of HSP 89α mRNA. Steady state levels of HSP 70 mRNA were increased in pancreatic carcinoma (tumor and connective tissue cells) and in chronic pancreatitis (connective tissue cells and residues of exocrine acinar cells). HSP 89β and ubiquitin B were constitutively expressed at high levels in pancreatic tissue from all three groups; HSP 89β mRNA was found in cells of parenchymal and stromal origin. A strong correlation was found between the expression of HSP 70 and the expression of transforming growth factor β1. The finding that HSPs are differentially expressed in pancreatic cancer, compared to normal pancreas and chronic pancreatitis tissue, and the cancer specifity of HSP 89α suggest that HSPs play a specific role in the pathogenesis of pancreatic cancer, e.g., by participating in regulatory processes or in tumor immunity, as proposed previously.