Background: Few allergic reactions to grape are reported in the literature. In some cases an association with peach and cherry allergy was observed. No IgE-mediated reactions to wine have been described, and no grape major allergens have yet been identified. Objective: We describe several severe reactions to grape or wine. We characterized the grape major allergens and tried to identify the allergen in wine. Methods: We collected documented histories of allergic reactions to grape and wine. Grape allergens were identified by means of SDS-PAGE and immunoblotting and purified by means of HPLC. Using amino acid sequencing and mass spectrometry, we identified the family of proteins to which the allergens belong. Cross-reactivity with peach and cherry was evaluated by means of cross-wise inhibition experiments. Results: Eleven patients with reactions to grape and 3 with anaphylactic reactions to wine were recruited. The major allergens were an endochitinase 4A and a lipid-transfer protein (LTP) that was homologous to and cross-reactive with peach LTP. A 24-kd protein homologous to the cherry thaumatin-like allergen was a minor allergen. Endochitinase 4A is very likely the allergen in vino novello and in vino Fragolino. Conclusions: Grape and wine might cause severe allergic reactions in sensitive patients. The major allergens of grape are endochitinase 4A, which is also the allergen of wine, and an LTP cross-reacting with the peach major allergen. (J Allergy Clin Immunol 2003;111:350-9.)