Background: Nebulized lidocaine enables dosages of oral corticosteroids to be tapered in the treatment of severe asthma. Objective: We sought to investigate the effect of lidocaine on T cells from patients with allergic asthma. Methods: PBMCs and CD4⁺ T cells were isolated from 6 patients with asthma and house dust mite allergy. PBMCs were cultured with lidocaine for up to 7 days and then stained with propidium iodide to evaluate the involvement of apoptosis. In addition, the viability of CD4⁺ T cells when cultured with lidocaine was investigated. Effects of lidocaine on proliferative response, mRNA expression, and protein production of IL-5 and IFN-γ by PBMCs were investigated after stimulation with Dermatophagoides farinae , purified protein derivative, and phorbol 12-myristate 13-acetate plus calcium ionophore. The effects of lidocaine on the proliferative response of steroid-insensitive PBMCs from 6 nonallergic donors induced by preculture with IL-2 and IL-4 were also investigated. Results: No significant increase in the staining of PBMCs with propidium iodide was observed in the presence of 100 μmol/L lidocaine. The viability of CD4⁺ T cells was not significantly affected by culture with lidocaine at this concentration. However, lidocaine inhibited, in a dose-dependent manner, the proliferative response and mRNA expression and protein production of IL-5 and IFN-γ of PBMCs stimulated with D farinae , purified protein derivatives, or phorbol 12-myristate 13-acetate plus calcium ionophore. Preincubation of PBMCs with IL-2 and IL-4 significantly decreased the inhibitory effects of both corticosteroids and lidocaine compared with that after preincubation with medium alone. Conclusion: Lidocaine has immunoregulatory effects on T cells. Therefore, lidocaine might be studied as an anti-inflammatory agent in the treatment of severe steroid-dependent asthma. (J Allergy Clin Immunol 2002;109:485-90.)