A well-organized network of varicose fibers was revealed throughout the frontal and temporal cortex of adult humans with specific antisera against histamine. The densest network of fibers was seen in lamina I, where varicose fibers were seen to run in parallel to the overlying pia mater. Electron microscopic immunohistochemistry revealed histamine-immunostaining in granules in a small number of nerve fibers and varicosities. Hypothalamic samples obtained from autopsy brains of adult humans revealed numerous histamine-immunoreactive nerve cell bodies in the posterior basal hypothalamus in and around the tuberomammillary nucleus. The results suggest that a histaminergic neuronal system reminiscent of that described in rodents is present in human brain.