BACKGROUND: Impaired folate metabolism has been suggested as a potential risk factor for the development of asthma and atopic disease. However, there have been conflicting reports on the potential association between atopic disease and a common polymorphism of the methylene-tetrahydrofolate reductase (MTHFR)-gene, a well-known marker of impaired folate metabolism. OBJECTIVES: The aim of this study was to investigate the association between the MTHFR (C677T) polymorphism and different outcome variables of asthma and atopic disease. METHODS: This study was a population-based study of 1189 participants aged 15-77 years living in Copenhagen, the Capital of Denmark. Examinations included measurements of specific IgE and skin prick tests against inhalant allergens, metacholine bronchial hyper-reactivity, and serum eosinophilic cationic protein, and a self-administered questionnaire about diagnoses and symptoms of allergy and asthma. In addition, participants were genotyped for the MTHFR (C677T) polymorphism. RESULTS: None of the examined outcomes were significantly associated with the MTHFR (C677T) polymorphism. CONCLUSIONS: The results of this study using detailed objective markers of atopic disease do not support the hypothesis that impaired folate metabolism as reflected by the MTHFR genotype is involved in the development of atopic disease.