We examined the effect of acute third intraventricular (IVT) injections of either saline or NPY (0.95. 3.0, 9.5, or 30.0-mu-g in 1-mu-l) on the 1-, 4-, and 22-hour postinjection food and water intake of female obese (fa/fa). heterozygous lean (Fa/fa). and homozygous lean (Fa/Fa) Zucker rats. None of the doses of NPY had an effect on either food or water intake of fa/fa rats. A significant increase of food intake was seen in Fa/Fa rats at 1 and 4 hours after the 3.0-mu-g injection of NPY and at 1, 4, and 22 hours after the 9.5-mu-g injection of NPY. Both 3.0 and 9.5-mu-g of NPY also stimulated 1- and 4-hour postinjection food intake of Fa/fa rats. although this effect was significant only at 4 hours after the 3.0-mu-g dose. NPY had a less reliable effect on water intake: 3.0-mu-g of NPY stimulated 1-hour postinjection water intake of Fa/fa rats and 4-hour postinjection water intake of Fa/Fa rats. These results indicate that lean. but not obese Zucker rats, respond by eating more to centrally administered NPY. This deficit is similar to the effects seen with IVT insulin injections and may be a result of a common receptor-mediated mechanism.