An enhanced production of hypothalamic neuropeptide Y (NPY) now appears to underlie a number of hyperphagia syndromes. However, the role of NPY in the hyperphagia induced by hypothalamic lesions has not yet been explored. Here, hypothalamic lesions were induced in mice by administration of goldthioglucose (GTG) and brain sections were stained immunocytochemically for NPY without pretreatment with colchicine. NPY-immunoreactive somas were visible in the hypothalamus of only one of eight control mice but were identified in the hypothalami of six of seven mice with GTG lesions. This suggests that GTG lesions cause an enhanced production of NPY, perhaps due to interruption of fibers from arcuate dopaminergic neurons that normally inhibit NPY+ cells. Thus, hypothalamic lesions may provoke hyperphagia by stimulating the production of NPY.