OBJECTIVE: To determine the effect of adding intravenous theophylline (administered as aminophylline) to nebulizations of albuterol and intravenous methylprednisolone in adults hospitalized for acute asthma. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: Inpatient service of a tertiary-care, university teaching hospital. PATIENTS: 21 adults (22 to 48 years old)--10 in the aminophylline group and 11 in the placebo group. INTERVENTIONS: Nebulized albuterol, 2.5 or 5.0 mg every 0.5 to 4 hours; intravenous methylprednisolone, 60 mg every 6 hours; and either individualized doses of aminophylline or placebo for 48 hours. MEASUREMENTS: Forced expiratory volume in 1 second (FEV1), the number of "as needed" albuterol nebulizations and total dose, asthma symptom scores, and adverse effects. RESULTS: At admission from the emergency department, the mean +/- SD baseline FEV1 was 49% +/- 19% of the predicted value in the aminophylline group and 43% +/- 13% of the predicted value in the placebo group. The improvement in FEV1 at 3 hours was greater in the aminophylline group (29% +/- 23% compared with 10% +/- 10% in the placebo group; mean difference, 19 percentage points; 95% CI, 3 to 35 percentage points; P = 0.023). At 48 hours, FEV1 was 75% +/- 19% of the predicted value in the aminophylline group and 58% +/- 15% of the predicted value in the placebo group (mean difference, 17 percentage points; CI, 0.2 to 34.8 percentage points; P = 0.048). Aminophylline-treated patients required fewer nebulizations of albuterol (10.3 +/- 3.8 compared with 16.4 +/- 5.3; mean difference, -6.1; CI, -10.3 to -1.8) and less total dosage (34 +/- 16 mg compared with 70 +/- 34 mg; mean difference, -36 mg; CI, -60.6 to -11.3 mg P = 0.02). No statistical differences were observed in asthma symptom scores or frequency of adverse effects. CONCLUSIONS: Individualized doses of intravenous theophylline added to frequent nebulizations of albuterol and intravenous methylprednisolone appear to benefit adults admitted to the hospital with acute asthma and are well tolerated when serum concentrations are maintained in the therapeutic range.