Total and partial isolations of the hypothalamo-pituitary unit were accomplished in the male rat using a new neurosurgical knife. Endocrine function was examined 75-90 days later. The major findings included evidence that a) the isolated hypothalamo- pituitary unit is capable of responding to ether stress, although at a submaximal level, b) differential effects may be obtained from animals with total isolations depending upon the amount of neural tissue included in the knife cut, c) some of the neural affercnts which influence the ACTH-rclcasing principles of median eminence origin ascend from caudal regions of the CNS and in the hypothalamus traverse a path within 1 mm of the midline, and d) separation of the medial from lateral hypothalamic areas at the level of the ventromedial nucleus without involvement of both fornix columns does not lead to hyperphagia and obesity. © 1968 S. Karger AG, Basel.