Food intake is regulated by many endogenous substances, such as peptides and neurotransmitters. in the central nervous system. Based on the clinical observation that some antidepressants and antipsychotics with antihistaminic activity stimulate food intake and increase body weight, histamine has been thought to be an anorectic agent. Several lines of evidence suggest that histamine decreases food intake via H-1-receptors (H1R) at least in the ventromedial hypothalamus or the paraventricular nucleus. Recently, mutant mice lacking H1R were generated and the interaction between the histaminergic system and leptin-induced suppression of food intake was evidenced by using these mice. In regulating food intake, histamine is indicated to functionally associate with neuropeptide Y, peptide YY, and bombesin. However, the question remained as to why the circadian variation in the level of histamine is inversely correlated to the pattern of feeding. (C) 2001 Elsevier Science B.V. All rights reserved.