The histaminergic projection from the hypothalamus to the superior col
liculus was examined immunohistochemically in the cat brain using an a
ntibody to histamine. The source of histaminergic fibers in the brain
is a group of neurons in the posterior hypothalamus, located primarily
in ventrolateral and periventricular regions and collectively referre
d to as the tuberomammillary nucleus. All laminae of the superior coll
iculus-including the superficial, intermediate, and deep layers, as we
ll as the central gray-were blanketed with histamine-immunoreactive ax
onal fibers. Overall, labeling in the superior colliculus was moderate
ly dense compared to other locations in the cat brain, with some varia
tion in fiber density. Individual labeled fibers resembled histaminerg
ic fibers described previously in the brain. Labeled axonal fibers sho
wed infrequent branching and were beaded with numerous en passant vari
cosities that were typically 1 mum or smaller, but as large as 2.5 mum
in diameter. Varicosity size differed significantly at different dept
hs in the colliculus. The histaminergic projection appears to be separ
ate from a previously reported, apparently non-histaminergic projectio
n from neurons in the dorsal hypothalamic area to discrete regions of
intermediate and deep colliculus. These results indicate that the hist
aminergic projection from the tuberomammillary nucleus of the hypothal
amus projects extensively throughout the superior colliculus. Histamin
e, which is believed to act as a neuromodulator in the brain, is in a
position to influence sensory and motor-related processes in every lay
er of the cat superior colliculus.