There is a high coexistence of substance abuse in humans with eating disorders. One theory offered to account for this fact is that a common biochemical substrate may exist that mediates both processes. Brain neuropeptide Y (NPY) is one neurochemical system that might contribute to these separate, yet related, problems. To clarify the role of NPY in mediating reward processes and the possible interaction between reward and feeding, the present study examined the effects of injecting NPY bilaterally into the perifornical hypothalamus (PFH) vs. the nucleus accumbens (NAC) on intake of preferred vs. non-preferred food types, as well as on conditioned place preference (CPP) learning. NPY (24, 78, 156 and 235 pmol/side) stimulated intake of both regular powdered chow and sucrose when injected into the PFH, but not the NAC. A CPP that was negatively correlated with food intake occurred with the low (24 pmol/side) dose of NPY in the PFH, while a CPP that was not correlated with food intake was produced with the same dose in the NAC. The extent of the CPPs produced by NPY injection in both brain sites mirrored that produced by peripheral injection of amphetamine (2.5 mg/kg). These results indicate that NPY elicits reward-related behavior, but not feeding, from the NAC, and both behaviors from the PFH. However, the feeding effect derived from the PFH appears to overshadow a rewarding effect derived from this site. Considered together, these findings suggest that altered NPY functioning in both brain regions may contribute to some of the pathophysiological processes observed in eating disordered patients who have additional proclivities for substance abuse.