Neuropeptide Y (NPY) is a 36 amino‐acid peptide. It is localized within the brain but is also present peripherally. It is a well substantiated orexigenic peptide with several other endocrine and behavioural effects. In this study NPY mRNA levels were measured, using the polymerase chain reaction amplification technique, in the hypothalamus of pre‐obese (unweaned 13‐day‐ old), young (weaned 28‐day‐old) and adult (11‐week‐old) obese fa/fa rats and compared to those of lean age‐matched controls. Before weaning, pre‐obese pups had the same NPY mRNA levels as controls. After weaning NPY mRNA levels were increased 2‐fold in young 28‐day‐old and 4‐fold in adult obese rats, relative to corresponding controls. When adult obese rats were intracerebroventricularly‐treated with ovine corticotropin‐releasing hormone (oCRF) for 7 days, they stopped gaining body weight elative to vehicle‐infused obese controls. Upon measuring NPY mRNA levels in the hypothalamus of these two groups of animals, it was shown that the high NPY mRNA levels of vehicle‐treated (control) obese rats were decreased by 3‐fold following the intracerebroventricular oCRF administration. It is proposed that: 1) hypothalamic NPY may play a role in the establishment and maintenance of the genetic obesity syndrome of the fa/fa rat, and 2) hypothalamic NPY could be partly regulated by central CRF.