Several studies provided evidence of innate interferons (IFNs) regulating T(H)2 cytokine production using purified CD4(+) memory cells and T(H)2 polarisation via interleukin-4 (IL-4). Vitally, none of these previous studies examined IFN attenuation of T(H)2 responses to allergen or antigen. This study therefore sought to investigate the abrogation of specific allergen- and antigen-stimulated T(H)2 response in peripheral blood mononuclear cells (PBMC) derived from 12 sensitised individuals by IFN-beta and IFN-lambda. PBMC were cultured in the presence of house dust mite (HDM) allergen, rhinovirus (RV), influenza vaccine and tetanus toxoid (TT)+/-either IFN-beta or IFN-lambda for 3 and 5 days. IFN-gamma, IL-5 and IL-13 protein levels were measured by ELISA. Quantitative PCR (qPCR) was used to investigate induction of genes involved in control of T(H)2 cytokines. No alteration in T(H)1 IFN-gamma allergen/antigen response was observed with addition of IFN-beta or IFN-lambda. Consistent abrogation of T(H)2 response to HDM and influenza was observed with IFN-beta at both time points; attenuation was observed by day 5 with RV and TT. IFN-lambda had no consistent effect on T(H)2 production except in the presence of RV (multiplicity of infection=5); a decrease in IL-5 alone was observed in the presence of trivalent inactivated influenza vaccine. GATA binding protein 3 (GATA3) and suppressors of cytokine signalling3 mRNA were differentially regulated in HDM and influenza-stimulated cultures+/-IFN-beta. We concluded that IFN-beta produced a strong and consistent abrogation of T(H)2 cytokine production in the presence of a range of allergen and antigen stimulants.