The most important symptoms caused by food additives are urticaria and angioedema, but rhinitis, asthma and gastrointestinal disturbances are also reported. Only seldom food additives have been shown to induce symptoms in other organs such central nervous system or joints and with a sparse objective evidence. In this study, we report two cases of unusual reactions to food additives (tartrazine and benzoates) involving mainly the central nervous system (headache, migraine, overactivity, concentration and learning difficulties, depression) and joints (arthralgias), confirmed with diet and double blind challenge. The possible pathogenetic mechanisms are also discussed.