Nerve fibers and terminals immunoreactive for cholecystokinin (CCK) were demonstrated in the nucleus of the solitary tract (NTS) of the rat using light and electron microscopic immunocytochemistry. The following morphological and biochemical evidence suggests that CCK in the NTS seems to be of extrinsic, most probably vagal, origin: (1) axon fragments of the intracranial vagus were identified by immunostaining on their way to the solitary tract; (2) CCK-immunostaining could be localized in nerve terminals in the nucleus of the solitary tract, where only a very few immunopositive dendrites or cell bodies were present; and (3) transecting the major neuronal afferents (via solitary tract and/or more laterally) resulted in a complete disappearance of radioimmunoassayable CCK from the nucleus of the solitary tract.