Histamine-induced food intolerance is not IgE-mediated. Skin-prick testing and specific IgE to food allergens are typically negative. Food rich in histamine or red wine may cause allergy-like symptoms such as sneezing, flush, skin itching, diarrhoea and even shortness of breath. The suspected reason is a diminished histamine degradation based on a deficiency of diamine oxidase. As diamine oxidase cannot be supplemented, a histamine-free diet was implemented to reduce histamine intake. Forty-five patients with a history of suffering from intolerance to food or wine (n = 17) and chronic headache (n = 28) were put on the diet over months to years. Fish, cheese, hard cured sausages, pickled cabbage and alcoholic beverages had to be avoided. Complaint intensity and drug-use per week prior to and 4 weeks after a histamine-free diet were compared. After 4 weeks on the diet 33/45 patients improved considerably (P < 0.01), eight of them had total remission. In 12/45 patients, however, no changes in symptoms were observed. Symptoms of food or wine intolerance significantly decreased (P < 0.02; treatment of choice), headaches decreased in frequency (P < 0.001), duration and intensity. After eating histamine-rich food symptoms were reproducible and could be eliminated by anti-histamines in most patients. These data indicate the role of histamine in food and wine intolerance and that histamine-rich food causes a worsening of symptoms in patients suffering from chronic headaches. Results obtained support the hypothesis of a deficiency of diamine oxidase in patients with intolerance to food or wine.