The c-fos gene product is a 55 kd nuclear protein bound to a cellular protein, p39. Expression of the c-fos oncogene is complex in that increased expression occurs in cultured cells during undifferentiated growth but decreased during terminal differentiation. We studied c-fos gene expression by streptavidin-biotin-peroxidase immunohistochemistry in pancreatic adenocarcinoma (N = 20), chronic pancreatitis (N = 9) and normal pancreas (N = 5). One islet cell tumour was included in the study. There was positive staining for c-fos oncoprotein in 15 of the 20 (75%) adenocarcinomas examined (9/12 moderate to poorly differentiated, 6/8 poorly differentiated). The single islet cell tumour investigated was also positive. Only 2 of 9 (22%) cases of chronic pancreatitis and 2 of 5 (40%) normal pancreata were positive. Stromal immunoreactivity was noted in all cancer cases while 5 of 9 (56%) chronic pancreatitis and 3 of 5 (60%) normal pancreas cases showed such staining. In conclusion, c-fos oncoprotein overexpression occurs more frequently in pancreatic cancers compared to chronic pancreatitis and normal pancreas. These findings are consistent with in vitro cell line studies of other cancers which showed increased expression of c-fos during undifferentiated growth.