Histamine (HA) is a biogenic amine, providing a number of functional roles throughout the body. HA release triggers inflammatory responses as a protective reaction against foreign pathogens. Released from basophils and mast cells in the periphery, HA causes increased vascular permeability and dilation of blood vessels to allow increased fluid infiltration into tissues which in turn induces swelling. Research designed to test the role of HA in mediating central nervous system (CNS) activity demonstrated that HA immunoreactive brain neurons actively fire action potentials and release HA during the wake phase but are essentially silent during sleep, supporting the hypothesis that increased HA tone is related to levels of wakefulness. Results of experiments investigating the effects of HA in the CNS, either through direct injection of HA or through pharmacological inhibition of its synthesis, show that increases in HA are positively correlated with amounts of wakefulness.