Unilateral coronal knife cuts through the ventrolateral pontine reticular formation produce overeating and overweight when combined with contralateral parasagittal knife cuts in the medial hypothalamus (MH). The knife cuts were in a position to sever fiber projections from the paraventricular nucleus to the hindbrain. The present study used histochemical techniques to confirm that hyperphagia-producing knife cuts transect PVN-hindbrain fiber connections. In Experiment 1, adult female rats received a unilateral coronal knife cut in the ventrolateral pontine reticular formation. Horseradish peroxidase (HRP) was applied to the knife cut region and two to three days later brains were processed for the localization of neurons labeled with HRP. HRP-labeled neurons were found in the PVN, particularly in the caudal parvocellular region. Additional HRP-labeled neurons were observed in other medial hypothalamic areas but none were found in the ventromedial nucleus. HRP-filled cells were also found in the lateral hypothalamus, central nucleus of the amygdala, and in the nucleus of the solitary tract (NST). Many of the PVN projections to the hindbrain contain oxytocin and Experiment 2 determined if hyperphagia-inducing knife cuts sever PVN oxytocinergic fibers. Adult female rats received unilateral MH cuts, unilateral pontine cuts, or a contralateral combination of both cuts. One to eight days later the brains were processed for immunocytochemistry. The MH cuts and pontine cuts were found to interrupt descending oxytocinergic fibers. Taken together, these results support the hypothesis that interruption of a direct PVN-hindbrain oxytocinergic projection is responsible for the hypothalamic hyperphagia-obesity syndrome. However, the results do not rule out the involvement of a multisynaptic pathway or additional neurochemical systems.