Changes in the level of expression of glucose-6-phosphate dehydrogenase (G6PD) within propyl nitrosamine-induced preneoplastic and neoplastic lesions in F344 rats and Syrian golden hamsters were investigated using an immunohistochemical approach. Previously demonstrated increases in G6PD activity in rat liver and hamster pancreatic foci of altered cells were revealed as being due to elevation in the quantity of enzyme protein, suggesting an underlying change in gene expression. Furthermore, strong positive binding of G6PD antibody in thyroid, lung, urinary bladder and kidney lesions indicated that increase in this enzyme protein might be a common marker for neoplastic alteration, regardless of organ. While the function of elevated G6PD may be related to growth requirements, the finding that preneoplastic lesions in some cases bind more strongly than more malignant populations suggests additional involvement of the enzyme in other biochemical pathway(s) relevant to tumorigenesis.