Pituitary prolactin (PRL) secretion is inhibited by dopamine (DA) released into the portal circulation from hypothalamic tuberoinfundibular DA (TIDA) neurons. Ames (df/df) and Snell (dw/dw) dwarf mice lack PRL, GH and TSH, abrogating feedback and resulting in a reduced hypophysiotropic TIDA population. In Ames df/df, ovine PRL administration for 30 d during early postnatal development increases the TIDA neuron number to normal, but 30 d PRL treatment of adult df/df does not. The present study investigated the effects of homologous PRL, administered via renal capsule pituitary graft surgery for 4 or 6 m, on hypothalamic DA neurons in adult Snell dw/dw mice using catecholamine histofluorescence, tyrosine hydroxylase (TH) immunocytochemistry (ICC), and bromodeoxyuridine (BrdU) ICC. PRL treatment did not affect TIDA neuron number in normal mice, but 4 and 6m PRL-treated dw/dw had significantly increased (p0.01) TIDA (area A12) neurons compared to untreated dw/dw. Snell dwarfs treated with PRL for 6 m had more (p0.01) TIDA neurons than 4m PRL-treated dw/dw, but lower (p0.01) numbers than normals. Periventricular nucleus (area A14) neuron number was lower in dwarfs than in normals, regardless of treatment. Zona incerta (area A13) neuron number was unchanged among phenotypes and treatments. Prolactin was unable to induce differentiation of a normal-sized A14 neuron population in dw/dw. BrdU incorporation was lower (p0.01) in 6m PRL-treated normals than in 6m PRL-treated dwarfs in the subventricular zone of the lateral ventricle and in the dentate gyrus, and lower (p0.05) in 4m untreated dwarfs than in 4m untreated normals in the median eminence and the periventricular area surrounding the third ventricle. Thus, a PRL-sensitive TIDA neuron population exists in adult Snell dwarf mice when replacement uses homologous hormone and/or a longer duration. This finding indicates that there is potential for neuronal differentiation beyond early developmental periods and suggests plasticity within the mature hypothalamus.