This study examined the effect of aerosolized isoproterenol and oral theophylline on pulmonary function in cystic fibrosis (CF) to determine how often these drugs are beneficial and whether there is a correlation between response to isoproterenol and response to oral theophylline. After obtaining baseline pulmonary function tests before and after isoproterenol aerosol, 12 patients with CF were put on a double-blind trial of high-dosage theophylline (10 mg/kg three times per day) or placebo for four weeks and were then switched to the alternate regimen for the next four weeks. Patients had weekly evaluations of pulmonary function and plasma theophylline determinations. Gastrointestinal side effects were common with theophylline. The responses to aerosolized bronchodilators were inconsistent from week to week. After aerosolized bronchodilator, five of 12 patients had an average increase of 10% or more in FEF45%-55% and FEFT70%-80%. While taking oral theophylline, five patients had a 10% or more decrease in FEF45%-55% and six patients had a decrease in FEF70%-80%. We conclude that there was no concorrdance between response to isoproterenol and theophylline, and that adrenergic and methylxanthine drugs must be used with caution in patients with CF.