Headache can be induced by histamine in wine in patients suffering from histamine intolerance, a disease characterized by impaired histamine degradation based on reduced diamine oxidase activity or a lack of the enzyme. Diamine oxidase is localized in the jejunal mucosa and is the most important enzyme metabolising histamine. It is competitively inhibited by alcohol and numerous drugs. In preliminary investigations, assessment of diamine oxidase levels gave decreased activity (0.03 nKat/l) in patients with histamine intolerance compared to healthy controls (0.07 nKat/l). In pregnancy, diamine oxidase levels are known to be about 500-fold elevated, giving mean levels of 25.0 nKat/l. Other biogenic amines such as phenylethylamine or serotonin may be causative for wine/food-induced headache. In experimental models, headache has been induced by histamine infusion as well as red wine provocation. Histamine-induced headache is a vascular headache likely to be caused by nitric oxide which probably represents a key molecule in vascular headaches. A histamine-free diet is the treatment of choice for patients with histamine intolerance and chronic headache. To start treatment, an antihistamine (H1 blocker) for 14 days as well as a histamine-free diet for at least 4 weeks are recommended. Clinical improvement to the diet as well as in vitro tests for plasma histamine and diamine oxidase in the serum as well as vitamin B6 levels have to confirm the diagnosis. As supportive treatment, a vitamin B6 (pyridoxal phosphate) substitution appears useful in histamine-intolerant patients as pyridoxal phosphate seems to be crucial for diamine oxidase activity. Histamine intolerance, based on reduced diamine oxidase activity or a lack in the enzyme is causative for wine/food-induced chronic headache. According to the localization of diamine oxidase in the jejunal mucosa, histamine intolerance is primarily a disease of intestinal origin. A histamine-free diet is the treatment of choice in histamine-intolerant patients suffering from chronic headache. In addition, it is also important to avoid diamine-oxidase-blocking drugs and alcohol which act as inhibitors of diamine oxidase. As avoidance of histamine-rich food is simple, inexpensive and harmless treatment, histamine-containing food such as cheese and alcoholic beverages should be labeled.