Purpose: To determine whether intravenously administered theophylline, when added to frequently nebulized albuterol and intravenously administered methylprednisolone, benefits children hospitalized with severe asthma. Design: Prospective, randomized, placebo-controlled, parallel-group, double-blind study. Setting: Inpatient pediatric service at a tertiary-care teaching hospital. Patients: Twenty-one children 5 to 18 years of age. Interventions: All patients received 2.5 to 5.0 mg of nebulized albuterol every 20 minutes to every 6 hours, intravenously administered methylprednisolone (1 mg/kg every 6 hours), and either intravenously administered theophylline (as aminophylline) or placebo for 36 hours. Serum theophylline concentrations were maintained between 55 and 110 μmol/L (between 10 and 20 μg/ml) by adjusting loading doses and continuous infusion rates. Measurements and main results: Forced expired volume in 1 second (FEV1) and clinical score were measured at 0, 1, 3, 6, 12, 24, and 36 hours after the start of each individual study. The total number of nebulizations, total albuterol dosage, adverse effects, and duration of hospital stay were recorded. Twelve children received theophylline and nine recelved placebo. The two group did not differ significantly in age, sex, or baseline FEV1. In both groups, clinical score significantly improved from baseline by 12 hours, and FEV1 by 24 hours (p<0.05). There were no significant differences between the groups in FEV1 or clinical score at any of the measured time points. There were no significant differences in rate of improvement in FEV1, total number of nebulizations, total albuterol dosage, or duration of hospital stay. Adverse effects were mild and infrequent and did not differ significantly between the two groups. Conclusions: Theophylline, at therapeutic concentrations, did not additionally benetit children hospitalized with severe asthma who were being treated frequently with nebulized albuterol and with methylprednisolone intravenously.