The sulfite family of food additives has been implicated in the pathogenesis of wine-induced asthma. However, the evidence supporting this is weak, and because wines have many hundreds of components, nonsulfite-associated mechanisms may also play a role.The aim of the study was to assess the potential sensitivity of persons with asthma to nonsulfite components in wine by using low-sulfite wine challenges.Sixteen adults with a strong history of wine-induced asthma were challenged with both low-sulfite red and white wines and wine-placebo drinks. Challenges were performed double blind, using a Latin square design, with lung function being assessed before the challenge and at 5, 10, 15, 30, and 60 minutes after the challenge. Subsequently, single-blind challenges with high-sulfite white wine were also completed in 10 individuals whose lack of reactivity to low-sulfite white wine suggested possible reactivity to sulfite additives.The mean FEV1; forced expiratory flow, mid-expiratory phase; and peak expiratory flow of subjects to low-sulfite red and white wines and red and white placebo wines were not significantly different. Furthermore, with a predetermined criterion of a fall in FEV1 of more than 15% representing a positive challenge, only one individual exhibited a positive reaction in the presence of a negative response to placebo. Only 2 of the 10 test individuals who were challenged with a high-sulfite wine demonstrated a marked and rapid fall in FEV1. Reactivity to low-sulfite wines appears to occur only in a small number of individuals who report sensitivity to wines, suggesting that the sulfite additives may be the major cause of wine-induced asthmatic reactions. However, direct challenge with high-sulfite wine revealed only 2 clear reactions in this asthma cohort.Wine-induced asthma appears to be a complex phenomenon and may involve several mechanisms that are codependent.