A study was made of six patients with Melkersson-Rosenthal syndrome (MRS) to establish the aetiological role of foodstuffs and/or additives and the possible associated immunological alterations. In all cases Melkersson-Rosenthal syndrome (MRS) was diagnosed both clinically and histologically, excluding other causes of orofacial granulomatosis (OFG). A detailed study of possible triggering factors was performed in all patients. Blood analysis, x-rays and cultures, were always within normal limits, with the exception of the finding of circulating immune complexes (CICs) in three patients with facial palsy associated, and C-reactive protein positivity in two patients who presented persistent labial oedema. All patients were subjected to skin-prick tests with common inhalant allergens and with foods when sensitization to foods were suspected, and patch tests with European Standard Series and pastry components, organic dyes, perfumes and fragrances series. The results were negative in all cases. When asymptomatic, the patients were subjected to a double-blind oral challenge, under placebo control, with additives (monosodium glutamate, tartrazine, sulfites, erythrosine, paraoxybenzoate, sodium benzoate, lactose, aspirin, and annate), which was again negative. In no case did the patients refer the appearance of outbreaks with exposure to foods or contactants, and the course of the disease was unaffected by exclusion diets and the elimination of contactants. To conclude, we observed no sensitization to foods, additives or contactants in our patients. Likewise, there were no antecedents of atopy or hereditary predisposition related to the aetiopathogeny of MRS. The significance of the CIC encountered only in patients with facial paralysis remains to be established, due to the limited number of patients studied.