Propafenone is a new membrane-stabilizing antiarrhythmic agent that structurally resembles the beta-adrenergic receptor antagonist, propranolol. To determine the potential asthmogenicity of this new drug, pulmonary function, airway reactivity to methacholine, blood pressure, the electrocardiogram, and plasma concentrations were measured in 12 patients with mild intermittent asthma after 48 to 72 hours of treatment with placebo and with oral propafenone in low dosage (150 mg every eight hours) and high dosage (300 mg every eight hours) in a double-blind crossover manner. The forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow over the middle half of the FVC (FEF25-75%), heart rate, and blood pressure during the three regimens of treatment were not significantly different; however, the QRS interval on the ECG was significantly widened with both dosages of active drug, and the mean provocative dose of methacholine (+/- SE) required to reduce FEV1 by 20 percent (PD20) decreased from 3.0 +/- 0.6 mg/ml with placebo to 2.1 +/- 0.7 mg/ml with the high dosage of propafenone (p less than 0.01). The mean PD20 on the low-dose regimen was not significantly different from placebo or high-dose therapy. A potentially relevant increase in airway reactivity, as measured by a ratio of less than 0.5 for PD20 after treatment to PD20 after placebo, occurred in seven subjects with high-dose and in one subject during low-dose treatment (p less than 0.01). These data suggest that propafenone should be used with caution in patients with asthma and that bronchial provocation will provide a more sensitive measure of the asthmogenicity of a drug with beta-adrenergic receptor antagonist activity than pulmonary function tests. Moreover, use of bronchial provocation allows the selection of subjects with mild disease, thus reducing the risk of potentially severe bronchospasm.