Eighty-nine patients who presented to the hospital for treatment of acute episodes of asthma were randomly assigned to initial therapy with subcutaneously administered epinephrine or 1 of 2 combination regimens consisting of intravenously administered aminophylline and either subcutaneously administered of epinephrine or inhaled isoproterenol. During the first hour of treatment, as a group, the patients treated with the 2-drug regimens showed greater objective improvement than did patients who received epinephrine alone. This was particularly true for patients with either severe airway obstruction or a subtherapeutic theophylline concentration at the time of presentation. There were no differences in the heart rate and blood pressure responses to the 3 regimens, and symptoms consistent with drug side effects were not reported more frequently by patients treated with 2 drugs. Thus, the combination of sympathomimetics and aminophylline appear more effective, and no more toxic, than epinephrine alone for the initial treatment of acute episodes of asthma.