Mepyramine-theophylline-acetate (MTA), a theophylline derivative combined with an antihistamine, is used to treat patients with asthma. A double-blind, randomized, prospective, parallel-group study was conducted to evaluate the efficacy and safety of MTA in the treatment of asthmatic crisis in children 2 to 6 years of age. Forty patients with mild-to-moderate asthma were admitted to the study. The MTA group received 8 mg/kg per day of MTA by mouth in three divided doses for 7 days. The other group received 50 microL/kg per day of placebo in three divided doses for 7 days. Salbutamol (albuterol) syrup was used as the rescue drug if manifestations of asthma persisted. Both the MTA group and the placebo group had similar demographic characteristics at baseline. Both groups showed improvement of the asthma symptoms (cough, dyspnea, hypoventilation, and wheezing), as evaluated by the investigators at days 3 and 7. Patient diary scores showed earlier improvements in the MTA group than in the placebo group. Both groups showed improvement in peak flow at days 3 and 7 (P = 0.005). The control group used more doses of salbutamol than the MTA group on days 2 through 6 and globally (mean +/- SD, 6.79 +/- 9.11 doses vs 1.29 +/- 2.23 doses). The improvements in the placebo group were thought to be due to salbutamol. Three MTA patients dropped out of the trial, one because the parents felt that the treatment was not effective and two because of gastrointestinal manifestations (epigastric discomfort and vomiting). In the placebo group, two patients dropped out. One patient had epigastric discomfort and the other had to be treated in the emergency department for an exacerbation of the asthma. We conclude that MTA may be a good therapeutic option for the treatment of asthmatic crisis in children 2 to 6 years of age.