Because of reports of drug tolerance occurring with chronic use of adrenergic agents in asthma, we investigated cardiopulmonary responsiveness to ephedrine and to the beta-2 agent, tebutaline, following chronic drug administration for periods up to one year. With chronic drug administration baseline (prior to daily medication) FEV increased 19% in the terbutaline group and 3.5% in the ephedrine group. An additional increase of FEV above baseline of 23% for terbutaline and 12% for ephedrine was noted after daily medication. Terbutaline also had a longer duration of effect; peak response after ephedrine occurred at 2 hr while terbutaline effect was maximal at 3 to 4 hr. There was no evidence for reduced responsiveness to the bronchodilator actions of either drug at any time. Despite prolonged use, both drugs continue to increase heart rate and pulse pressure moderately following ingestion, with a peak effect occurring at 3 hr; however, pulse pressure widened after terbutaline because of a diastolic fall, while the major effect of ephedrine was to increase systolic pressure. Baseline blood pressure, particularly diastolic, declined progressively with continued drug use. No evidence of cardiac, ehpatic, renal, or ophthalmologic toxicity or change in need for other bronchodilator agents was noted during the study with either drug.