R ecently, epigenetic-mediated mechanisms — which involve heritable changes in gene expression in the absence of alterations in DNA sequences — have been proposed as contributing to asthma. In this issue of the JCI, Hollingsworth and colleagues report on the effect of prenatal maternal dietary intake of methyl donors on the risk of allergic airway disease in offspring in mice and show that these effects involve epigenetic regulation (see the related article beginning on page 3462). Supplementation of the maternal diet with methyl donors was associated with greater airway allergic inflammation and IgE production in F1 and, to some extent, F2 progeny. Site-specific differences in DNA methylation and reduced transcriptional activity were detected. If these findings are confirmed, a new paradigm for asthma pathogenesis may be emerging.