Evidence of a neurohumoral factor capable of stimulating insulin and glucagon secretion was found in perfusates from ventrolateral hypothalamus (VLH) of rhesus monkeys. The perfusates from the VLH were collected via push-pull cannulas and injected into the peripheral circulation. Increase in portal insulin and glucagon was observed following the injection of six different perfusates. The amount of insulin released from isolated rat islets incubated with perfusates was significantly increased at glucose concentrations > 5 mM. The perfusates from the VLH appear to have effects on insulin and glucagon secretion that are opposite those of somatostatin.