We examined effects of theophylline withdrawal in 17 adult asthmatics whose symptoms were well controlled under a treatment of a combination of theophylline and inhaled beclomethasone dipropionate (iBDP). We measured daily symptoms, daily peak flow values, spirometry, peripheral blood eosinophil count (EOS), and serum eosinophil cationic protein (sECP) at intervals of 1-3 weeks for 3 months after theophylline withdrawal. Twelve patients experienced exacerbation of asthma (exacerbation group), whereas the remaining 5 patients exhibited no symptoms (stationary group). In the exacerbation group, forced expiratory volume in 1 sec (FEV1) and percent vital capacity (% VC) gradually decreased until exacerbation of asthma, and the extent of these decreases within the first week after the withdrawal was greater compared with that at later than the third week. V25/HT decreased in both the exacerbation and stationary groups. In particular, the extent of the velocity of expiratory flow at 25% of the vital capacity/height (V25/HT) decrease in the exacerbation group was much greater than that of FEV1 or % VC in this group. Neither EOS nor sECP changed significantly during the clinical course in any patient. The rapid decrease in FEV1 and % VC after the withdrawal suggests that under treatment with iBDP, theophylline causes direct bronchodilating effects on smooth muscle, rather than anti-inflammatory effects. These results also suggest the importance of theophylline on peripheral as well as central airways.