The changes in airway caliber and plasma cyclic-AMP levels after intravenously administered aminophylline, and the effect of DL- and D-propranolol on these responses have been investigated in a double-blind manner in normal subjects. Aminophylline 5.6 mg/kg was given intravenously over a 10-min period and the airway response was measured as change in specific airway conductance (delta SGaw) in the body plethysmograph. In the initial study in 6 subjects, orally administered placebo or propranolol was followed 2 h later by intravenously administered aminophylline. Neither placebo nor propranolol alone caused any change in SGaw at 2 h. After placebo, intravenously injected aminophylline produced a 30% increase in SGaw, reaching a peak 5 min after injection. This response was equivalent to 77% of the maximal response to 400 micrograms inhaled albuterol in the same subjects. After propranolol, the airway response to aminophylline was attenuated, with a 53% reduction in delta SGaw at the time of peak response. In a further study on 6 subjects, intravenously given aminophylline produced a 25% increase in SGaw and a 51% increase in plasma cyclic-AMP levels after placebo tablets. Pretreatment with 40 and 80 mg DL-propranolol caused a dose-dependent reduction of both the airway and plasma cyclic-AMP response to aminophylline. The airway response to aminophylline was not attenuated by D-propranolol so the effect of DL-propranolol is thought to be due to beta-adrenoceptor blockade. The absence of any detectable change in SGaw after DL-propranolol suggests there is little resting sympathetic tone to the airways in normal subjects. In the absence of sympathetic stimulation, the rapid response to aminophylline is unlikely to be due to phosphodiesterase inhibition. The attenuation of the airway and cyclic-AMP response by propranolol suggests that part of the action of aminophylline may be due to beta-agonist activity.