1. Neuropeptide Y (NPY) gene expression in human phaeochromocytomas was investigated by measuring the levels of NPY mRNA and NPY-immunoreactivity (NPY-IR) in human phaeochromocytoma tissues in comparison with those in normal human adrenal tissues. 2. The amounts of NPY mRNA and NPY-IR in human phaeochromocytomas were 18 and 93 times higher, respectively, than those in normal adrenal glands. In contrast, beta-actin gene expression was similar in human phaeochromocytomas to that in normal adrenal glands. 3. The amount of NPY mRNA relative to total cellular RNA was 6-fold higher in phaeochromocytoma tissues than in normal human adrenal medulla, suggesting increased NPY gene expression in the tumour cells. 4. Induction of differentiation of PC12 rat phaeochromocytoma cells by compounds, such as dexamethasone and nerve growth factor, resulted in a marked increase in the NPY mRNA level. 5. These findings suggest that NPY gene expression is increased in well-differentiated human phaeochromocytoma cells. Its high level of expression could be responsible for the marked overproduction of NPY by this tumour.