Histamine is the neurotransmitter of photoreceptors in insects and other arthropods. As a photoreceptor transmitter, histamine acts on ligand-gated chloride channels. Another type of histamine receptor has been indicated in the insect central nervous system by binding pharmacology. This receptor is similar to the mammalian H 1 receptors, which are G-protein coupled and thus utilize a second messenger system. The distribution of histamine-immunoreactive (HAIR) neurons has been studied in a few insect species: cockroaches, locust, crickets, honey bee, blowflies, and in Drosophila. In addition to its presence in photoreceptor cells, histamine is distributed in a rather small number of neurons in the insect brain. Many of these neurons have extensive bilateral arborizations that innervate several distinct neuropil regions, notably in the protocerebrum. Some patterns of histamine distribution are seen in all the species. On the other hand, the number and morphology of neurons differ between the studied species, and several major neuropils (central body, antennal lobes, mushroom bodies) are suppliedby HAIR neurons in some species, but not in others. Thus it appears that there are some species-specific functions of histamine and on others that are preserved between species. Some of the histaminergic neurons may constitute wide field inhibitory systems with functions distinct from those of neurons containing ␥-amino butyric acid (GABA). Novel data are presented for Drosophila and the cockroach Leucophaea maderae and a comparison is made with published data on other insects.