CD4+ T-cells are considered as pivotal in orchestrating the airway inflammation in asthma through the actions of their cytokines. Current hypothesis suggests that the anti-asthma effect of theophylline may be due to its anti-inflammatory actions, although the exact mechanisms remain unclear.The in vitro effect of theophylline on cytokine gene expression in peripheral blood CD4+ T-cells in normal subjects was compared with that of dexamethasone and salbutamol. CD4+ T-cells were cultured with phytohaemagglutin and phorbol myristate acetate in the presence of different concentrations of theophylline (10 -8 ±10 -3 M or 0.0018±180 mg . mL -1 ) in one group of subjects (n=8), dexamethasone (10 -9 ±10 -6 M or 0.39±390 ng . mL -1 ) in a second group (n=8) and salbutamol (10 -9 ±10 -4 M or 0.00058±58 mg . mL -1 ) in a third group (n=8). Gene expression of interleukin (IL)-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-c was semiquantified by reverse transcription-polymerase chain reaction.Suppressed expression of IL-3 (36.9%), IL-4 (38.8%), GM-CSF (24.6%) and IFN-c (37.7%), but not of IL-5, was only seen with theophylline at a concentration of 10 -3 M (180 mg . mL -1 ) (p<0.05) and not at lower concentrations. In contrast, dexamethasone caused a dose-dependent suppression of transcription of all cytokines, with 39.5% for IL-3, 84.4% for IL-4, 40.6% for IL-5, 50.9% for GM-CSF and 31.8% for IFN-c at 10 -6 M (390 ng . mL -1 ) (p<0.05±0.001). Salbutamol did not suppress gene expression of any of the cytokines at the concentrations examined.These data suggest that cytokine gene expression of CD4+ T-cells is not affected at therapeutic concentrations of theophylline and salbutamol, but its suppression is likely to be an important mechanism underlying the therapeutic effect of corticosteroids in asthma.